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\begin{document}

\title{Pupil versus 1 st Purkinje capsulotomy centration with femtosecond
laser: long term outcomes with a sinusoidal trifocal lens}



\author[1]{Ramiro M. P. C. Salgado}%
\author[2]{Paulo F. A. A. S. Torres}%
\author[2]{António A. P. Marinho}%
\affil[1]{Centro Hospitalar Universitario de Santo Antonio}%
\affil[2]{Universidade do Porto}%


\vspace{-1em}



  
  \date{June 08, 2024}


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\selectlanguage{english}
\begin{abstract}
Purpose: To assess the role of femtosecond laser-assisted capsulotomy
centration in the long-term intraocular positioning of a multifocal
intraocular lens. Design: Prospective comparative study. Methods: A
total of 60 eyes of 30 patients underwent femtosecond laser--assisted
Refractive Lens Exchange (RLE). \emph{} For every patient, capsulotomy
centration was randomly performed according to pupil centre (PC) in one
eye and first Purkinje reflex (FPR) in the other. The intraocular lens
(IOL) positioning, visual acuities, spherical equivalent, internal
aberrometry and quality of vision were assessed and compared at 3 years'
follow-up between groups (PC and FPR). Results: Intraocular lens
positioning showed a statistically significant difference between
groups, with a closer centration to the visual axis in the FPR patients
(p=\textless{}0.001). Internal aberrometry showed higher values in the
PC capsulotomy centration group (p\textless{}0.01). Conclusions: First
Purkinje reflex (FPR) centered capsulotomy is associated to a closer
centration of the IOL to the visual axis.%
\end{abstract}%



\sloppy


\emph{Title Page}

\emph{Original Article -- Clinical Science}

\emph{Title}

\textbf{Pupil versus 1\textsuperscript{st} Purkinje capsulotomy
centration with femtosecond laser: long term outcomes with a sinusoidal
trifocal lens}

\emph{Author 1}

Name: Ramiro M. P. C. Salgado

Academic degrees: MD

Institutional affiliation: Departamento de Oftalmologia do Hospital da
Arr\selectlanguage{ngerman}ábida. Hospital de Santo António, Centro Hospitalar e Universitário
do Porto, Portugal

\emph{Author 2}

Name: Paulo F. A. A. S. Torres

Academic degrees: MD, PhD

Institutional affiliation: Departamento de Oftalmologia do Hospital da
Prelada. Universidade do Porto, Portugal

\emph{Author 3}

Name: António A. P. Marinho

Academic degrees: MD, PhD

Institutional affiliation: Departamento de Oftalmologia do Hospital da
Luz Arrábida. Universidade do Porto, Portugal

\emph{Corresponding author:} Ramiro M. P. C. Salgado, Departamento de
Oftalmologia do Hospital da Luz Arrábida, Praceta Henrique Moreira 150,
4400-346 Vila Nova de Gaia, Portugal. Phone: 00351915677244. Fax:
00351224003046. Email:\emph{rsalgadoft2@gmail.com}

\emph{Running title}

\textbf{Femtosecond laser capsulotomy centration}

The authors declare that they have no known competing/conflicts of
interest that could have appeared to influence the work reported in this
paper.

The authors declare that there are no funding sources involved in work
reported in this paper.

\emph{Abstract}

\emph{Purpose} : To assess the role of femtosecond laser-assisted
capsulotomy centration in the long-term intraocular positioning of a
multifocal intraocular lens.

\emph{Design} : Prospective comparative study.

\emph{Methods} : A total of 60 eyes of 30 patients underwent femtosecond
laser--assisted Refractive Lens Exchange (RLE). For every patient,
capsulotomy centration was randomly performed according to pupil centre
(PC) in one eye and first Purkinje reflex (FPR) in the other. The
intraocular lens (IOL) positioning, visual acuities, spherical
equivalent, internal aberrometry and quality of vision were assessed and
compared at 3 years' follow-up between groups (PC and FPR).

\emph{Results} : Intraocular lens positioning showed a statistically
significant difference between groups, with a closer centration to the
visual axis in the FPR patients (p=\textless{}0.001). Internal
aberrometry showed higher values in the PC capsulotomy centration group
(p\textless{}0.01).

\emph{Conclusions} : First Purkinje reflex (FPR) centered capsulotomy is
associated to a closer centration of the IOL to the visual axis.

Keywords : FLACS, capsulotomy, IOL centration, femtosecond, cataract

\textbf{TEXT}

INTRODUCTION

The role of capsulotomy in the IOL final position has long been
established, \textsuperscript{1, 2, 3} being consensually accepted that
an optimal (curvilinear, continuous, 360º IOL edge overlapping)
capsulotomy is required to obtain the best positioning of the IOL, by
ensuring long-term stability and centration, taken the IOL-capsular bag
interaction, namely, capsular adherence and time-related retraction.
Femtosecond laser-assisted capsulotomy has been regarded as an
improvement in this matter, as it is associated to higher levels of
effectiveness, predictability, and accuracy.\textsuperscript{4,
5}Intraocular lens (IOL) centration is of paramount importance in
multifocal IOL~implantation, since adequate IOL positioning is required
for attaining the goals of best performance and patient
satisfaction.\textsuperscript{6}

Ideally, the IOL should centered on the visual axis, pursuing the
biometry goal (usually emmetropia) in purely refractive terms. In
practical terms, the vertex normal is used instead of the theoretical
visual axis, which correlates to the first Purkinje
reflex.\textsuperscript{7, 8} Additionally, in the case of multifocal
IOLs, pupil center must also be considered for adequate IOL positioning,
since pupillary diameter directly impacts on the different foci
(distance, intermediate and near, for trifocal lenses), influencing
these IOL's performance.\textsuperscript{9} However, the optics of the
eye are not ideal, which renders it impossible to line up the optical
centers of all ocular elements. This evidence is translated, amongst
other concepts, into the angle alpha and angle kappa; whereas the former
reports to the angle formed between the visual axis and the optical
center, the latter, in particular, is of relevance when considering the
implantation of a multifocal IOL, as it relates to the angle formed
between the theoretical visual axis and the pupil center. For practical
purposes, the kappa angular measure has been substituted for a more
modern and functional equivalent, which is the chord mu, as described by
Chang and Waring;\textsuperscript{10} this is a two-dimensional vector
measured across the corneal surface from the center of the pupil to the
coaxially sighted, subject-fixated corneal light reflex (CSFCLR). The
CSFCLR can be described as a line-of-sight guided corneal reflex when
the patient fixates on the coaxial lights of the surgical microscope,
closest to the first Purkinje reflex.

In this line of thought, a large k angle may constitute a
contraindication for multifocal IOL implantation, as this condition
inhibits an efficient combination of the two reference centration
points; although a well-defined limit is not established, it is commonly
accepted for most authors that chord mu should be inferior to 500
micra.\textsuperscript{6} Regarding IOL implantation, it is currently
recommended that the lens should be manually centered halfway between
the pupil center and the visual axis (or first Purkinje
reflex),\textsuperscript{8, 10} thus conjugating both requirements.
However, this common gesture has two main pitfalls. Firstly, it assumes
that the IOL will stay in that position, not contemplating the
IOL-capsular bag interaction along time; this interaction depends on
several factors such as lens- and capsular bag-related conditions.
Secondly, pupil center changes with pharmacological pupillary dilatation
prior to surgery traduced by a significant increase of chord mu
length;\textsuperscript{11} therefore, intraoperative pupil center is
farther away from the ideal visual axis, which compromises the accuracy
of such positioning endeavor.

This study's protocol proposed to manually center the IOL inner
diffractive circle in the alignment of along the first (CSFCLR) and
fourth Purkinje reflexes during surgery, as recommended by some
authors.\textsuperscript{8, 12}

The methodology of IOL centration assessment varies in the literature.
Methods based on measuring the distance between the IOL optic edge to
the dilated pupil have the disadvantage of disregarding the fact that
dilation is often asymmetric and affects normal geometry, consequently
it does not reproduce the physiological status. Some sophisticated
methods of measuring IOL decentration using Scheimpflug imaging, and
anterior segment ocular coherence tomography (OCT) have been described.
These methods have their own limitations. Measurements from Scheimpflug
imaging can be inaccurate because of magnification and distortion
effects from the Scheimpflug camera and OCT imaging requires 3D
algorithmic analyses.\textsuperscript{13, 14}

This study proposes to assess the influence of capsulotomy centration on
the long term IOL positioning, by comparing femtosecond laser-assisted
pupil-centered versus first Purkinje reflex-centered capsulotomy.

METHODS

This prospective randomized comparative 2-armed study was approved by
the Ethics Committee at Hospital da Luz Arrabida (HLA), Porto, (ref:
04/2019/CES) and was conducted in accordance with the ethical principles
stated in the ``Declaration of Helsinki'', with signed informed consent
given by each patient. All patients were proposed to undergo femtosecond
laser--assisted RLE in both eyes for presbyopia correction. For each
patient, capsulotomy centration was randomly assigned to pupil centre in
one eye and first Purkinje reflex in the other. All patients had surgery
between October 3, 2019, and March 2, 2020, at Hospital da Luz Arrabida
(HLA). All surgeries were performed at HLA by a single comprehensive
surgeon (R.S.) using the Centurion Vision (Alcon Laboratories, Inc.)
phacoemulsification system and the LDV Z8 femtosecond laser platform
(Ziemer, Inc.). The IOL power was calculated to achieve emmetropia in
all cases.

Inclusion and Exclusion Criteria

Patients were excluded from the study if they had previous ocular
surgery, preoperative corneal astigmatism more than 0.75D, chord \selectlanguage{greek}µ
\selectlanguage{english}\textgreater{} 500 \selectlanguage{greek}µ\selectlanguage{english}m, ocular pathology, corneal abnormalities, and an
endothelial cell count less than 2000 cells/ mm2. Also, posterior
capsule opacification above minimal was considered a bias for this
study's conclusions and constituted an exclusion criterium.

Measurement Procedures and Study Devices

The Galilei G4 is a tomography system based on dual Scheimpflug imaging
and Placido-disc technology. Participants were asked to look at the
fixation point, blink, and open their eyes widely before each image
acquisition. Manual alignment of the red crosshair to the 4 Purkinje
dots, corresponding to the first Purkinje reflex (FPR) in the cornea, is
performed and mesopic (mean of 5.5 lux) pupil diameter and center (PC)
are acquired. The device calculates chord mu length, from FPR to PC;
this chord mu is apparent, as it measures the distance between the first
Purkinje reflex and the pupil center viewed through the cornea. Galilei
G4 displays several maps, enabling visualization of IOL central
diffractive rings, along with FPR (corneal vertex), pupil and optical
centers, and limbus-to-limbus imaging (Figure 1).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Fig. 1 Top view imaging with Galilei G4}

\emph{a:} Four dots hair cross (first Purkinje reflex). \emph{b:} Pupil
center (small white cross), angle kappa and chord mu data (Galilei G4
software).

Aberrometry assessment was performed with VX120 (Visionix, Inc.); this
is a multimodal platform, combining Scheimpflug and Placido-disc
technology, together with an Hartmann-Shack aberrometer which directly
measures corneal and total ocular aberrations, inferring the internal
aberrations from the aforementioned data. All measurements were
performed under the same illumination conditions (mesopic pupil at 5.5
lux).

Regarding distance measurement between protocol landmarks and reference
points, the authors have chosen a hybrid measuring method. For IOL
positioning assessment, eye photographs were obtained with Galilei G4 at
the protocol timepoint (36 months postoperatively) and subsequently
processed with the Fiji's Image J program (software version
2.0.0-rc-49/1.51a), which allowed several measurements of the distance
between FPR, PC, OC and IOL center. Regarding IOL centration, the
postoperative first Purkinje reflex was defined as the reference point,
as it closely relates to the visual axis. Henceforth, decentration was
determined according to the measured distances between FPR and the IOL
centre (inner diffractive circle). Calibration was accomplished by using
the constant limbus horizontal size as a reference, allowing pixel
measurements conversion into millimetres for each eye.

Biometry was performed using optical interferometer Galilei G6 (Ziemer
Ophthalmic systems AG) and every subsidiary examination (such as OCT,
corneal topography, specular microscopy, etc.) was conducted by a
technician, unaware of the type of capsulotomy centration. Participants'
manifest refractions were collected (sphere, cylinder, and spherical
equivalent), with objective refractive errors assessed by an
autorefractor (Topcon Co. Ltd.).

Posterior capsule opacification was assessed at the 3 years
postoperative visit, after pupil dilation, with a modified version of
the Evaluation of Posterior Capsule Opacification (EPCO), as described
by some authors. For that matter, retroillumination images were obtained
with Visionix and subsequently processed with Image J, which allowed
identification, marking and calculation of density areas by performing
pixel counts. The density of the opacification behind the IOL was
clinically graded as follows: 0 = none; 1 = minimal; 2 = mild;
3=moderate; 4=severe. Then, individual PCO score for each eye was
determined with Evaluation of Posterior Capsule Opacification (EPCO) by
multiplying the density of the opacification (graded from 0 to 4) by the
fractional PCO area involved behind the IOL optic.

Patient reported outcomes were assessed using a 5-point Likert scale
questionnaire regarding the level of satisfaction (graded from 1 -- very
dissatisfied; 2 -- dissatisfied; 3 - neither satisfied nor dissatisfied;
4 - satisfied; 5 - very satisfied), whereas quality of vision was
determined by a 4-point Likert scale questionnaire comprising the
existence of visual disturbance or photic phenomena, graded from 0
(none) to 4 (very high).

Lens transparency was assessed by slitlamp examination and assigned a
grade according to the Lens Opacities Classification System (LOCS) III.
Corneal topography and tomography were determined using a Placido - dual
Scheimpflug device (Galilei G6). Macular spectral-domain optical
coherence tomography was performed with a modular ophthalmic imaging
platform (Carl Zeiss).

Postoperatively, all patients were evaluated at 1 day, 1 week, and at 1,
6, 12, 24 and every year thereafter and 36 months. Visual acuities were
assessed with Snellen chart (for distance) and reading Jaeger chart (for
near and for intermediate, with reading line conversion for the latest,
keeping the same visual angle) and ultimately converted to LogMAR
notation. Manifest refractions were collected (sphere, cylinder and
spherical equivalent), with objective refractive errors assessed by an
autorefractor (Topcon Co. Ltd.). At each visit, the uncorrected (UDVA)
and corrected (CDVA) distance visual acuities at 6 m, uncorrected (UIVA)
and corrected intermediate (CIVA) visual acuities at 60 cm, and
uncorrected (UNVA) and corrected (CNVA) near visual acuities at 40 cm
were measured. In the present study, and according to the proposed
protocol, only the long-term (at the 3-years' visit) postoperative data
are presented. All patients filled in the quality of vision and
satisfaction level tests at 36 months.

Intraocular Lens

The Acriva\textsuperscript{UD}~Trinova\textsuperscript{TM} (VSY
Technology) is a plate-haptic, diffractive aspheric hydrophobic acrylic
IOL with a blue light--filtering multifocal design. According to the
manufacturer, Sinusoidal Vision Technology (SVT\selectlanguage{ngerman}®) has the aim of
reducing photic phenomena.

\textbf{Surgical Technique}

One experienced surgeon (R.S.) performed all the surgeries. Capsulotomy,
corneal incisions and lens fragmentation were accomplished by
femtosecond laser (LDV Z8, Ziemer, Switzerland), followed by
emulsification, irrigation and aspiration of lens material performed
with the phacoemulsification machine (Centurion Vision, Alcon
Laboratories, USA).

Capsulotomy was centered on the pupil center (PC) or the first Purkinje
reflex (FPR), according to the protocol's randomized assignment. For
this matter, in the FPR group of patients, the coaxially sighted
subject-fixated corneal light reflex (CSFCLR) was marked on the cornea
surface with an ink marker, immediately before femtosecond docking, and
capsulotomy was centered on this point. In the PC group, pupil
centration was achieved automatically with LDV OCT imaging upon docking
and capsulotomy performed henceforth (Figure 2A and B).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Fig. 2 Centration points visualization with the surgical
microscope (\emph{A}) and with LDV Z8 femto machine after docking
(\emph{B})}

\emph{a:} CSFCLR marked with ink (blue arrow) on the cornea surface (the
left coaxial smaller light). \emph{b:} LDV Z8's display of a pupil
centered capsulotomy preset (blue arrow signalizing the CSFCLR, here
presented with an enlarged ink mark).

CSFCLR -= coaxially sighted subject-fixated corneal light reflex

After implantation, the IOL was positioned in the capsular bag with its
innermost diffractive ring in alignment with the first (CSFCLR) and
fourth Purkinje reflex, while the patient was asked to fixate on the
coaxial light of the surgical microscope; after pressing the optic
against the posterior capsule, the chamber was sealed with the IOL optic
seated against the capsular bag.

Statistical Analysis

Comparisons were based on paired and unpaired Student t-test, or
non-parametric analysis tests when the equality of variances was not
observed. Correlations were assessed using Pearson's correlation test,
and the results were confirmed with a non-parametric test (Spearman
correlation test). All statistical tests were done using a significance
level of \selectlanguage{greek}α \selectlanguage{english}= 0.05.

The distance between the postoperative FPR and the IOL center, was
designated as the primary outcome, with internal aberrometry, UDVA, UIVA
and UNVA and patient-reported quality of vision selected as secondary
outcomes.

The sample size was determined \emph{a piori} using G*Power, for a
difference test between two dependent means, using a significance level
of \selectlanguage{greek}α\selectlanguage{english}=0.05, a power of 90\%, and a medium to large, expected effect size.
The minimum number of subjects needed was 27. The statistical analysis
was performed using R (v. 4.3.0) in RStudio (v. 2023.03.1+446).

RESULTS

Preoperative Patient Data

Thirty-two patients had both eyes operated, achieving a total of 64 eyes
operated. Two of them were withdrawn from the study, as they did not
complete the 3 years follow up.

The study population included 19 (63.3\%) female and 11 (36.7\%) male
patients, with a mean age of 71\selectlanguage{ngerman}±7 years old (range 59 to 87). The mean
IOL power was +24.12±4.05 D (range 13.0 to 29 D). Table 1 shows the
patients' preoperative characteristics by capsulotomy centration: pupil
centration (PC) or first Purkinje reflex centration (FPR). There was no
statistically significant difference between the 2 groups
preoperatively.

\textbf{Table 1.} Patient demographic and clinical characteristics.\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\textbf{Parameter} & \textbf{Centration Point} & \textbf{Centration
Point} & \textbf{Centration Point}\tabularnewline
& Mean\selectlanguage{ngerman}±SD & Mean\selectlanguage{ngerman}±SD & \emph{p value}\tabularnewline
& \textbf{PC} & \textbf{FPR} &\tabularnewline
UDVA (logMAR) & 0.32\selectlanguage{ngerman}±0.12 & 0.32\selectlanguage{ngerman}±0.11 & 0.917\tabularnewline
CDVA (logMAR) & 0.02\selectlanguage{ngerman}±0.06 & 0.02\selectlanguage{ngerman}±0.06 & 0.980\tabularnewline
Spherical Equivalent (D) & 1.33\selectlanguage{ngerman}±2.01 & 1.37\selectlanguage{ngerman}±2.03 & 0.326\tabularnewline
Total corneal astigmatism (D) & 0.56\selectlanguage{ngerman}±0.29 & 0.62\selectlanguage{ngerman}±0.34 &
0.469\tabularnewline
Nuclear sclerosis + & 0.12\selectlanguage{ngerman}±0.63 & 0.12\selectlanguage{ngerman}±0.59 & 0.836\tabularnewline
Axial length (mm) & 21.98\selectlanguage{ngerman}±1.80 & 21.84\selectlanguage{ngerman}±1.90 & 0.876\tabularnewline
Anterior chamber depth (mm) & 3.18\selectlanguage{ngerman}±0.21 & 3.18\selectlanguage{ngerman}±0.22 &
0.862\tabularnewline
White-to-white (mm) & 11.83\selectlanguage{ngerman}±0.30 & 11.87\selectlanguage{ngerman}±0.27 & 0.989\tabularnewline
chord mu (mm) & 0.250\selectlanguage{ngerman}±0.073 & 0.243\selectlanguage{ngerman}±0.070 & 0.339\tabularnewline
alpha distance (mm) & 0.428\selectlanguage{ngerman}±0.08 & 0.426\selectlanguage{ngerman}±0.080 & 0.424\tabularnewline
\bottomrule
\end{longtable}

CDVA = corrected distance visual acuity (6 m); D = diopters; FPR = first
Purkinje reflex centration; LogMAR = logarithm of the minimum angle of
resolution; PC = pupil center centration; SD=standard deviation; UDVA =
uncorrected distance visual acuity (6 m). +Lens Opacities Classification
System III grade

Postoperative data

As to the postoperative chord mu, there was no statistically significant
difference between the two groups (95\% CI: -0.004 to 0.017; p=0.182);
the same statistical findings regarding postoperative alpha distance
were registered (95\% CI: 0.000 to 0.00; p=0.067). Nevertheless, a
statistically significant difference was found between pre and
postoperative chord mu in each group (p\textless{}0.001), traducing a
shorter distance between PC and FPR after surgery. Furthermore, when
comparing the change in chord mu between groups, a statistically
significant difference was found (95\% CI: -0.026 to -0.002; p=0.022),
with a higher change in the PC group (Table 2).

\textbf{Table 2.} Comparison between pre and postoperative chord mu and
alpha distance\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Parameter (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Parameter (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Mean \selectlanguage{ngerman}± SD {[}95\%CI{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Mean \selectlanguage{ngerman}± SD {[}95\%CI{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{p value {[}Mean Dif 95\% CI{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{PC}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{FPR}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{alpha distance}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{Preop} \emph{Postop} Mean Dif. \selectlanguage{ngerman}± SD \emph{p value}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.428\selectlanguage{ngerman}±0.084 {[}0.396; 0.460{]} 0.355±0.057 {[}0.333;0.377{]} 0.073±0.055
{[}0.052;0.094{]} \emph{\textless{}0.001*}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.426\selectlanguage{ngerman}±0.080 {[}0.395; 0.456{]} 0.358±0.053 {[}0.338;0.378{]} 0.067±0.050
{[}0.049;0.086{]} \emph{\textless{}0.001*}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{0.424 {[}-0.007; 0.003{]}} \emph{0.067 {[}0.000; 0.007{]}}
\emph{0.111} \emph{{[}-0.012; 0.001{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{chord mu}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{Preop} \emph{Postop} Mean Dif. \selectlanguage{ngerman}± SD \emph{p value}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.250\selectlanguage{ngerman}±0.073 {[}0.222; 0.277{]} 0.158±0.032 {[}0.146;0.171{]} 0.091±0.083
{[}0.060;0.123{]} \emph{\textless{}0.001*}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.243\selectlanguage{ngerman}±0.070 {[}0.216; 0.269{]} 0.165±0.039 {[}0.150;0.180{]} 0.077±0.070
{[}0.051; 0.104{]} \emph{\textless{}0.001*}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{0.339 {[}-0.022; 0.007{]}} \emph{0.182 {[}-0.004;0.017{]}}
\emph{0.022*} \emph{{[}-0.026; -0.002{]}}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

CI = confidence interval; Dif = difference; FPR = first Purkinje reflex;
Mean Dif., mean difference; PC = pupil center; SD, standard deviation.
*Statistically significant.

The mean postoperative IOL center (IOLC) -- FPR distance was 0,193\selectlanguage{ngerman}±0088
mm in the PC group, whereas it was 0,159±0,068 mm in the FPR group,
representing a statistically significant difference between the two
capsulotomy groups (mean difference: 0.034±0.046 mm; 95\% CI: 0.017 to
0.050; p\textless{}0.001). Likewise, a statistically significant
difference (mean difference: 0.015±0.025 mm; 95\% CI: 0.006 to 0.024;
p\textless{}0.01) was also found between groups regarding the IOLC -- OC
(optical center of the cornea). Considering IOLC -- PC (pupil center)
distance, no statistically significant difference was found between PC
and FPR capsulotomy centration (mean difference: 0.020±0.056 mm; 95\%:
0.000 to 0.040; p=0.064) (Table 3). Figure 3 illustrates the difference
in distance from IOL center to FPR between both eyes of the same
patient, with a different capsulotomy centration per eye.

\textbf{Table 3.} Postoperative landmarks and IOL distances at 3 years\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Parameter (mm)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Mean\selectlanguage{ngerman}±SD {[}95\%CI{]}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Mean\selectlanguage{ngerman}±SD {[}95\%CI{]}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\emph{p value {[}Mean Dif 95\% CI{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{PC}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{FPR}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
chord mu\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.158\selectlanguage{ngerman}±0.032 {[}0.146; 0.171{]} 0.355±0.057 {[}0.333;0.377{]} 0.193±0.088
{[}0.159; 0.226{]} 0.221±0.071 {[}0.194;0.248{]} 0.265±0.115 {[}0.222;
0.308{]}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.165\selectlanguage{ngerman}±0.039 {[}0.150; 0.180{]} 0.358±0.053 {[}0.338;0.378{]} 0.159±0.068
{[}0.133;0.185{]} 0.201±0.090 {[}0.167;0.260{]} 0.250±0.111 {[}0.208;
0.291{]}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\emph{0.182 {[}-0.004;0.017{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
alpha distance\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{{[}0.000; 0.007{]}}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{distance IOLC-FPR}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
{[}0.017; 0.050{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
distance IOLC-PC\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{{[}0.000; 0.040{]}}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{distance IOLC-OC}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
{[}0.006; 0.024{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

CI = confidence interval; Dif = difference; FPR = first Purkinje reflex;
IOL= intraocular lens; OC= optical center; PC = pupil center;
SD=standard deviation. *Statistically significant\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{Fig. 3 Postoperative landmarks with first Purkinje reflex
(\emph{A}) and pupil (\emph{B}) centered capsulotomies}

\emph{a:} Center of IOL (red dot) closer to first Purkinje reflex (green
star) in a first Purkinje reflex capsulotomy centration. \emph{b:}Center
of IOL farther from to first Purkinje reflex (red dot) and closer to
pupil center (small white cross) in a pupil center capsulotomy
centration.

As shown in Table 4, at the 3 years postoperative evaluation, the mean
UDVA was 0.01\selectlanguage{ngerman}±0.04 logMAR for the PC group and it was 0.01±0.04 logMAR
for the FPR group; the mean difference between groups was 0.00±0.04
(95\% CI: -0,02 to 0,01; p=0.662). We registered a mean postop UIVA of
0.02±0.04 logMAR for the PC group and a value of 0.02±0.05 logMAR for
the FPR group (mean diff.: 0.00±0.03, 95\% CI: -0.01 to 0.01; p=0.573),
whereas mean postop UNVA was 0.14±0.05 logMAR for the PC group and it
was 0.14±0.05 logMAR for the FPR group (mean diff.: 0.00±0.02, 95\% CI:
-0.01 to 0.00; p=0.645).

\textbf{Table 4.} Postoperative visual and refractive outcomes at 3
years (monocular)\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Parameter}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{Centration Point}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Mean\selectlanguage{ngerman}±SD {[}95\%CI{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Mean\selectlanguage{ngerman}±SD {[}95\%CI{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Mean\selectlanguage{ngerman}±SD {[}95\%CI{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{p value {[}Mean Dif 95\% CI{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{PC}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{PC}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{FPR}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
UDVA (LogMAR)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-0.01\selectlanguage{ngerman}±0.04 {[}-0.01;0.02{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-0.01\selectlanguage{ngerman}±0.04 {[}-0.01;0.03{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-0.01\selectlanguage{ngerman}±0.04 {[}-0.01;0.03{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{0.662} \emph{{[}-0.02;0.01{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
CDVA (LogMAR)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-0.01\selectlanguage{ngerman}±0.04 {[}-0.02;0.01{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-0.01\selectlanguage{ngerman}±0.03 {[}-0.02;0.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
-0.01\selectlanguage{ngerman}±0.03 {[}-0.02;0.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{0.712} \emph{{[}-0.01;0.02{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
UIVA (LogMAR)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.02\selectlanguage{ngerman}±0.04 {[}0.00;0.4{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.02\selectlanguage{ngerman}±0.05 {[}0.00;0.03{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.02\selectlanguage{ngerman}±0.05 {[}0.00;0.03{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{0.573} \emph{{[}-0.01;0.01{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
DCIVA (LogMAR)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.05\selectlanguage{ngerman}±0.05 {[}0.03;0.07{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.06\selectlanguage{ngerman}±0.05 {[}0.04;0.07{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.06\selectlanguage{ngerman}±0.05 {[}0.04;0.07{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{0.423} \emph{{[}-0.02;0.017{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
UNVA (LogMAR)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.14\selectlanguage{ngerman}±0.05 {[}0.12;0.16{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.14\selectlanguage{ngerman}±0.05 {[}0.12;0.16{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.14\selectlanguage{ngerman}±0.05 {[}0.12;0.16{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{0.645} \emph{{[}-0.01;0.00{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
DCNVA (LogMAR)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.16\selectlanguage{ngerman}±0.05 {[}0.14;0.18{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.15\selectlanguage{ngerman}±0.05 {[}0.14;0.17{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.15\selectlanguage{ngerman}±0.05 {[}0.14;0.17{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{0.592} \emph{{[}-0.01;0.02{]}}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Spherical Equivalent (D)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.05\selectlanguage{ngerman}±0.21 {[}-0.03;0.13{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.04\selectlanguage{ngerman}±0.18 {[}-0.03;0.11{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.04\selectlanguage{ngerman}±0.18 {[}-0.03;0.11{]}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\emph{0.573} \emph{{[}-0.02;0.04{]}}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

CDVA = corrected distance visual acuity (6 m); D = diopters; CI =
confidence interval; DCIVA = distance-corrected intermediate visual
acuity (at 60 cm); DCNVA = distance-corrected near visual acuity (40
cm); Dif = difference; FPR = first Purkinje reflex; LogMAR = logarithm
of the minimum angle of resolution; PC = pupil center; UDVA =
uncorrected distance visual acuity (6 m); UIVA = uncorrected
intermediate visual acuity (at 60 cm); UNVA = uncorrected near visual
acuity (40 cm)

The uncorrected distance visual acuity, the difference between UDVA and
CDVA and the postoperative refractive cylinder for both groups are shown
in Figure 4 (A, B and D). The accuracy was similar for both groups,
regarding the postoperative spherical equivalent (Figure 4C); in the FPR
group, 100\% of the eyes fell in \selectlanguage{ngerman}±0.50D range, compared to 96.7\% of the
eyes in the PC group. One eye (3.3\%) in the PC group presented with
negative postoperative spherical equivalent in the range of -0.51 to
-1.25D.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

\textbf{Fig. 4 Postoperative refractive outcomes}

\emph{a:} Uncorrected distance visual acuity.~\emph{b} : Uncorrected
distance visual acuity versus corrected distance visual acuity.~\emph{c}
: Spherical equivalent refraction accuracy.~\emph{d} : Postoperative
refractive cylinder (n=30 eyes in each group).

CDVA = corrected distance visual acuity; FPR = first Purkinje reflex; PC
= pupil center; UDVA = uncorrected distance visual acuity.

For the Evaluation of Posterior Capsular Opacification (EPCO) analysis,
based on picture quality, there were 60 eyes (of 30 patients) available
at 3-years of follow up. The mean PCO score of the EPCO analysis
was~0.338\selectlanguage{ngerman}±0.243 (range: 0.000 to 0.690) for the~PC group and~0.347±0.230
(range: 0.000 to 0.720) for the FPR group, reflecting no
statistical~difference between them~(mean diff.: -0.009±0.142, 95\%:
-0.060 to -0.041; p=0.725). Seven eyes (23.3\%) of the PC group and 6
eyes (20\%) of the FPR group did not display any signs of PCO, whereas
23 of the PC eyes (76.7\%) and 24 of the FPR eyes (80\%) displayed an
EPCO score from \textgreater{} 0 to 1 (none to minimal).

Regarding aberrometry data, a statistically significant difference was
found between groups for internal high-order (HOAs) aberrations (mean
diff.: 0.016±0.023 \selectlanguage{greek}µ\selectlanguage{english}m, 95\% CI: 0.008 to 0.024; p\textless{}0.01) and
for total internal root-mean-square (RMS) aberrations (mean diff.:
0.007\selectlanguage{ngerman}±0.008 \selectlanguage{greek}µ\selectlanguage{english}m, 95\% CI: 0.004 to 0.009; p\textless{}0.01), with higher
values in the PC group; comparison of low-order aberrations (LOAs)
between groups showed no statistically significant difference (mean
diff.: 0.004\selectlanguage{ngerman}±0.010 \selectlanguage{greek}µ\selectlanguage{english}m, 95\% CI: 0.000 to 0.007; p= 0.073).

A positive significant but weak correlation (p value\textless{}0.05;
R\textsuperscript{2}\textless{}0.05) was found between distance from the
IOL center to the visual axis (IOLC-FPR) and internal (HOAs and LOAs)
RMS in the total eye population (p\textless{}0.001;
R\textsuperscript{2}=0.38) (Figure 5).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}

\textbf{Fig. 5 Correlation between internal aberrations (RMS) and
distance IOLC -- FPR}

FPR = first Purkinje reflex; IOLC: intraocular lens center; PC = pupil
center; RMS = root mean square

Quality of vision (QoV) and satisfaction were slightly better with FPR,
but still not statistically significant, with a mean difference of
0.03\selectlanguage{ngerman}±0.56 (95\% CI: -0.17 to 0.23; p=0.745) for QoV and a mean
difference of -0.07±0.45 (95\% CI: -0.23 to 0.09; p=0.423) for the
satisfaction questionnaire.

DISCUSSION

Intraocular lens centration within the capsular bag is determined by
various factors on the long-term.\textsuperscript{15} Amongst them are
IOL and capsular bags characteristics which interact with each other;
IOL factors include the optic and haptic material,~the overall IOL
length in relation to the capsular bag diameter, and the inherent
ability of the haptics to withstand compressive forces of a contracting
capsular bag; capsular bag related factors include integrity, geometric
features (such as size and morphology) and capsulotomy features. It is
widely consensual the importance of a circular, continuous capsulotomy,
as well as its centration, which impacts on the long-term positioning of
the IOL.\textsuperscript{16} Furthermore, the point of capsulotomy
centration has been a topic of discussion, concerning the profile of
multifocal diffractive IOLs. This profile demands an optimization of the
IOL centration, eliciting the search for the best match of the eye's
several reference points and lines, along with the pupil's paramount
role; some recent studies have proposed different capsulotomy centration
points other than the classical pupil center.\textsuperscript{17, 18}

Also, postoperative changes to the capsular bag such as anterior
capsular contraction and posterior capsular opacification vary depending
on the IOL material and amount of anterior capsule overlap of the IOL's
edge.\textsuperscript{17} In this study, posterior capsular
opacification was none to minimal for both groups, thus not presenting
itself as a major factor influencing IOL positioning. Capsular bag
contraction exerts a force on the IOL and may lead to decentration.
Improved centration is perceived as one the features of femtosecond
laser-assisted capsulotomy, with increased efficacy and
accuracy.\textsuperscript{6, 19} Moreover, the low-energy femtosecond
laser device used in this study is associated to an absence of
intraoperative capsular-related complications (tags or ruptures), as
several recent studies demonstrate.\textsuperscript{20, 21}

Regarding the magnitude of IOL center -- visual axis decentration, a
distance of less than 0.25 mm is seldom noticeable and a multifocal IOL
would typically be described by most clinicians as ``well-centered''. A
decentration in the range of 0.25--0.50 mm is noticeable in a slit-lamp
examination, and it has been assumed that it is clinically
insignificant; however, this assumption lacks some clinical strong
evidence. Furthermore, not always is the visual axis (or its equivalent)
chosen as the reference point for centration assessment, but rather the
optical center or even the pupil center.\textsuperscript{22}

The present study shows modification of the IOL positioning along time,
traduced by a lens displacement towards the optical center of the
cornea; this fact is not influenced by the performed intraoperative
manoeuvre of manually centration of the IOL aligned with the visual axis
(as commonly recommended). This feature has been reported in the
literature and it is has been mostly described as an auto centration of
the IOL in the capsular bag,\textsuperscript{23} with many factors being
involved in this phenomena, mostly geometric at first hand. Furthermore,
our results show evidence that the choice of the reference centration
point regarding capsulotomy, influences the long-term positioning of the
IOL. Therefore, beyond strengthening the fact that the IOL tends to
adjust itself to the capsular bag (more than intraoperative IOL manual
positioning), this study shows that capsulotomy centration on the first
Purkinje reflex is associated to better IOL centration towards the
visual axis, as compared to pupil centration. This fact is translated
into a significant impact on aberrometric values, notwithstanding the
fact that it did not influence the quality of vision or patient
satisfaction scores, in this study. Our results also shows that the
refractive outcomes do not seem to be influenced by capsulotomy
centration. A possible explanation for this apparent asynchrony could be
assigned to the sinusoidal technology of the Acriva Trinova, which may
allow increased tolerance to deviations from the ideal aberrometry
profile.

In this study, only IOL centration was evaluated regarding IOL
positioning, as a sole variable impacting on performance outcomes.
Several publications point out to a reduced influence of tilt on
multifocal IOLs performance,\textsuperscript{24, 25} as opposed to a
significant impact of decentration in this type of intraocular lenses.
Nevertheless, in this context, there was never intention to minorize the
role of tilt on MIOL; rather than an oversimplification, the authors'
choice of this single approach (isolating the centration factor in the
context of IOL positioning) related to the feasibility of the IOL
decentration assessment with respect to visual axis.

At last, the present study has some pitfalls: it contemplates only one
type (plate-haptic) of IOL, restricting the evidence to this specific
design; tilt is not measured in this paper, as mentioned above;
aberrometry measurements were performed under a single (mesopic)
illumination condition; and a larger series is recommendable to
strengthen the evidence so far. However, this study does enhance the
long-term relevance of capsulotomy centration of multifocal IOLs as
close as possible to the visual axis, as a first-choice procedure when
performing refractive lens surgery, and further introduces a novel
marking procedure for achieving such purpose.

ACKNOWLEDGEMENTS

João Duarte Reis, MSc, Biostatistics, Coimbra, Portugal, provided
statistical support.

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2022;\textbf{10(12)} :3639-3646.\selectlanguage{english}
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