Download Double-C loop platform in combination with hydrophobic and

LABORATORY SCIENCE
Double-C loop platform in combination
with hydrophobic and hydrophilic acrylic
intraocular lens materials
Dimitriya Bozukova, PhD, Liliana Werner, MD, PhD, Nick Mamalis, MD, PhD, Laure Gobin, PhD,
Christophe Pagnoulle, PhD, Anne Floyd, MD, PhD, Erica Liu, MD, PhD, Shannon Stallings, MD, PhD,
Caleb Morris, MD, PhD
PURPOSE: To analyze the behavior of a new double-C-loop quadripod symmetrical intraocular lens
(IOL) platform combined with a hydrophilic lens material and a new hydrophobic glistening-free
acrylic lens material, Ankoris and Podeye, respectively, in silico (computer simulation), in vitro
(laboratory investigation), and in vivo (rabbit model).
SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA, and Physiol S.A.,
Liege, Belgium.
DESIGN: Experimental study.
METHODS: An in silico simulation investigation was performed using finite elements software, an
in vitro investigation according to the International Organization for Standardization (ISO119793:2012), and an in vivo implantation in a rabbit model with 4 weeks of follow-up. Postmortem
data were collected by Miyake-Apple gross examination and histopathologic analyses.
Biocompatibility and IOL centration were tested.
RESULTS: Both IOLs demonstrated statistically insignificant variations in posterior and anterior
capsule opacification and Soemmerring ring formation. They were well biotolerated with no signs
of toxicity, inflammation, or neovascularization. Axial and centration stability were noted in vitro and
in vivo as a result of significant contact between surrounding tissues and haptics and the posterior
portion of the optic.
CONCLUSION: The results suggest suitability of the double-C loop IOL platform for the
manufacturing of premium (ie, multifocal, toric, and multifocal toric) IOLs.
Financial Disclosure: Drs. Bozukova, Gobin, and Pagnoulle are employees of Physiol S.A., Liege,
Belgium. Dr. Pagnoulle has a proprietary interest in the tested intraocular lenses. No other author
has a financial or proprietary interest in any material or method mentioned.
J Cataract Refract Surg 2015; 41:1490–1502 Q 2015 ASCRS and ESCRS
Numerous investigations to evaluate the biomechanical stability of intraocular lenses (IOLs) have been
done. Some evaluate the biocompatibility of the lens
material.1–5 Others emphasize the influence of the
design on the degree of posterior capsule opacification
(PCO)6–11 and lens biomechanical stability.12,13
Early studies reported that hydrophobic acrylic
materials are associated with lower PCO rates as a
result of lens epithelial cell (LEC) regression after
approximately 1 month of implantation regardless of
the IOL design.2 Later studies demonstrated the
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Q 2015 ASCRS and ESCRS
Published by Elsevier Inc.
importance of a sharp posterior lens optic edge as a
major factor limiting the PCO rate.8,9 Rabbit studies
demonstrated that cell migration was prevented by
intimate mechanical contact between the sharp optic
edge and the capsular bag.
A 5-year clinical study compared the neodymium:
YAG (Nd:YAG) laser capsulotomy rates with 2 hydrophobic acrylic IOLs with a sharp optic edge and a
round optic edge and a hydrophilic acrylic IOL with
a sharp optic edge.14 The results suggested that the
combination of a sharp optic edge and a hydrophobic
http://dx.doi.org/10.1016/j.jcrs.2014.10.042
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LABORATORY SCIENCE: DOUBLE-C-LOOP COMBINED WITH HYDROPHOBIC AND HYDROPHILIC ACRYLIC IOLS
acrylic material was the most appropriate choice for
preventing optically significant PCO.
Contradictory results have been reported,6–11 probably due to differences in the geometries of the
analyzed square edges. This further confuses the situation, and the surgeon’s choice becomes even more
difficult, especially when premium IOLs are concerned because their optical performance can be
highly affected by undesirable cell proliferation and/
or lens misalignment. Indeed, abundant cellular proliferation or axial shift of the optic may lead to loss of
visual acuity, which can be particularly deleterious
with multifocal IOLs.15
Recently, Hirnschall et al.6 reported a 3-year
randomized trial of a plate-haptic IOL and a 3-piece
open-loop haptic toric IOL made of the same material.
The IOLs had comparable PCO rates and capsular bag
stability.
The latest studies assessed the effect of both lens material and lens optic design on the biocompatibility,
optic centration, and rotational and axial stability of
IOLs, particularly premium ones (eg, multifocal, toric,
and multifocal toric).6,14,16 For instance, Chang16
compared a silicone plate-haptic IOL with a hydrophobic acrylic C-loop model and reported better rotational stability of the hydrophobic C-loop version.
Other authors have reported the results of singlemodel clinical investigations of the biomechanical
stability of toric IOLs.17–19 The results indicate that silicone plate-haptic IOLs are prone to rotate by 5.56 degrees G 8.49 (SD),19 whereas hydrophobic acrylic
C-loop IOLs manifest rotation levels in the range of
3.2 G 2.8 degrees.17 However, it would be speculative
to conclude that the design or the material is a determinant for this result.
Intrinsically, a C-loop design might be prone to
rotate more easily in the direction opposite the haptic
orientation. However, contrary to plate haptics, they
provide more contact with the surrounding tissues.20
Recently, a new double-C-loop IOL (Physiol S.A.),
combining the advantages of C-loop haptics and a
symmetrical platform, was investigated clinically in
its hydrophilic acrylic version. Ninety-one patients
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(117 eyes) were included in the study, which reported
an absolute rotation of 2.5 G 2.06 degrees 12 months
after implantation.
The present study evaluated this IOL platform in
combination with a generic hydrophilic acrylic material or a proprietary hydrophobic acrylic glisteningfree material (Physiol S.A.21–23) using in silico
(computer simulation), in vitro (laboratory investigation), and in vivo (rabbit model) conditions. To our
knowledge, the results of these 3 investigational
methods are being presented for the first time. Biomechanical parameters are discussed in parallel with data
related to the capsular and uveal biocompatibility of
the test IOLs.
MATERIALS AND METHODS
Intraocular Lenses
Podeye is a monofocal aspheric IOL manufactured from a
hydrophobic acrylic glistening-free material (GF, Physiol
S.A.). Ankoris (technical name POD T, Physiol S.A.) is a
monofocal toric aspheric IOL manufactured from a hydrophilic acrylic material with a water uptake of 26%. Both
IOLs contain ultraviolet and blue-light filters (proprietary formula from Physiol S.A., WO2006074843 used for the hydrophilic acrylic material24) and are double-C-loop quadripodes
(Figure 1). The IOLs have an overall diameter of 11.4 mm,
an optic diameter of 6.0 mm, and anteroposterior angulation
of 5 degrees. The power of the tested IOLs was C23.5 diopters
(D), and the tested toric IOLs had a cylinder of 1.5 D.
In Silico Evaluation
Finite Elements Numerical Simulation Numerical simulation of the biomechanical behavior of the IOLs was performed by the finite element method using Samcef
Samtech software (Siemens). The Young modulus and the
geometry of the IOLs were introduced as key parameters.
The IOL mechanics were evaluated for different compression diameters simulating different capsular bag sizes for 2
conditions: “backed-up,” approximating the situation with
an intact capsule, and “free,” approximating the situation after Nd:YAG PCO treatment when the posterior capsule was
no longer intact. Radial compression forces were measured
at the horizontal plane; axial compression forces (Case 1)
and axial shift (Case 2) were measured at the vertical plane
(Figure 2). Gravity was not considered.
In Vitro Evaluation
Young Modulus The elasticity (Young) modulus of sample
Submitted: March 6, 2014.
Final revision submitted: October 9, 2014.
Accepted: October 13, 2014.
From Physiol S.A. (Bozukova, Gobin, Pagnoulle), Liege, Belgium;
the John A. Moran Eye Center (Werner, Mamalis, Floyd, Liu, Stallings, Morris), University of Utah, Salt Lake City, Utah, USA.
Corresponding author: Dimitriya Bozukova, PhD, Physiol S.A., Allee
des Noisetiers 4, 4031 Liege, Belgium. E-mail: d.bozukova@
physiol.be.
disks of 3.0 mm thickness and 6.0 mm in diameter from
the test and reference materials were tested with Instron
5566 and a static load cell of 500 N. The reference materials
were tested in their equilibrated state (conditioned in a
physiologic medium similar to the aqueous humor) after
processing, packaging, and sterilization similar to the IOLs.
Compression at a constant rate of advancement of the load
cell of 0.5 mm/min was applied. The data were interpreted
with Bluehill 2 software (Instron). The measurement was
performed in triplicate, and the mean values were used for
interpretation.
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Figure 1. Design of the hydrophobic and hydrophilic IOLs.
Scanning Electron Microscopy The optic edges of the dry
IOLs were analyzed by scanning electron microscopy
(SEM) (JSM 840A, Jeol Ltd).
Confocal Microscopy The topography of the IOL optic periphery was analyzed using a 3-dimensional optical profiler
confocal microscope (Sensofar PLU Neox, objective 20).
Haptic Compression ForceLRadial Compression Force
(FR) The force applied by the haptics to the capsular bag
is important for IOL rotational and refractive stability and
may have some effect on its resistance to PCO. The force
was determined with a compression force tester (MFC1385-IOL, O&O mdc Ltd.); the possible value variation was
less than 0.2% (method validation). Before the measurement,
the equipment was calibrated according to the standard
manufacturer’s procedure. Intraocular lenses in their original packaging state (1 per IOL model) were placed between
the 2 jaws, and the compression force, in milligrams force,
was measured for well diameters of 10.0 mm and 9.5 mm
corresponding to various capsular bag sizes. In all cases,
measurements were taken 30 seconds after haptic compression to give the haptic material time to relax. Ten samples
per IOL model were tested. Median standard deviations
(SDs) were calculated.
The test was performed in accordance with the procedure
recommended by the International Organization for Standardization (ISO) 11979-3.25
Axial Shift in Compression (Z) On compression, the haptics
of the IOLs may deform differently and, therefore, the IOL
optic may or may not remain at the initial position, moving
forward or backward along the optical axis. Determining the
axial shift experimentally aims at estimating the capability of
the IOL haptics to compensate for capsular bag size variations and enable a stable anteroposterior IOL position,
referred to as the effective lens position (ELP). This displacement was measured in air at 20 C G 2 C for all tested IOL
models (1 per IOL model) in their original packaging state
(hydrated or dried). The IOLs were placed in wells of 10.0
mm and 9.5 mm. Ten samples per IOL model were tested.
The axial shift was determined using an optical comparator
Figure 2. Representation of the 2 cases used for the finite elements
numerical simulation. Line with dashes represents the posterior
capsular bag (FR Z axial compression force; FR Z radial compression
force; Z Z axial shift).
with a precision of G 0.001 mm according to the procedure
described by ISO 11979-3.25
Angle of Haptic Contact or Degree of Haptic Contact The
angle of haptic contact is a measured approximation of the
total haptic contact with the supporting ocular tissue. A
high angle of haptic contact is associated with high interface
between the IOL and tissue, with a higher friction force
impeding IOL rotation. The angle of haptic contact was
measured in vitro according to the procedure recommended
by ISO 11979-3.25 Briefly, the IOL in its equilibrated state was
positioned in test wells with an overall diameter of 10.0 mm
and 9.5 mm. An image per condition was collected by optical
microscopy (XLI Cap software, Optica), and the angle of
haptic contact was then determined as the angle between
the points where the clearance between the loop and well
wall was 0.25 mm. A measuring device with an accuracy
of 0.5 degrees was used. Ten samples per IOL model were
tested. The result per IOL is presented as the sum of the angle
of haptic contact measured for the 4 haptics.
Optic Decentration (DX) Decentration of the IOL optic with
respect to the optical axis may be deleterious for visual acuity
because the IOL will no longer be in the optimum position.
Decentration was measured in vitro according to the procedure recommended by ISO 11979-3.25 The setup from the
angle of haptic contact test was used, and the optic decentration was measured as the distance between the optic center
and the center of the traced circle corresponding to the test
well diameter. Ten samples per IOL model were tested.
In Vivo Evaluation
Five New Zealand white rabbits of the same sex and
weighing between 2.4 kg and 3.2 kg were acquired from
approved vendors in accordance with the requirements of
the Animal Welfare Act for use in this study. An extra rabbit
was also ordered in case 1 of the study animals died. The animals were numbered consecutively from 1 to 6. They were
housed and cared for at the animal facility of the John A.
Moran Eye Center, University of Utah, Salt Lake City,
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Utah, USA. All rabbits were treated in accordance with the
guidelines of the Association for Research in Vision and
Ophthalmology, the Animal Welfare Act, and the Institute
for Laboratory Animal Research. The animals were quarantined for at least 7 days prior to the beginning of the study.
Their eyes were grossly checked for the presence of anomalies before the surgical procedures. The examination (performed by the same surgeon) was unremarkable in all eyes.
The hydrophobic IOL was implanted in the right eye of
the rabbits and the hydrophilic IOL in the left eye. The surgical procedures were performed by the same surgeon (N.M.)
using the Universal S3 OPMI 6-CFC, XY surgical microscope
(Carl Zeiss Meditec AG).
Surgical Technique Each animal was prepared for surgery
by pupil dilation with cyclopentolate hydrochloride 1.0%
and phenylephrine 2.5% drops, applied topically approximately every 5 minutes for 15 minutes. A drop of gatifloxacin
(Zymaxid) was also applied topically approximately
every 5 minutes for 15 minutes. Anesthesia was achieved
with an intramuscular injection of ketamine hydrochloride
(50 mg/kg) and xylazine (7 mg/kg) in a mixture of 7:1.
One drop of topical proparacaine hydrochloride was also
placed in each eye before surgery. Eye movement and animal respiration were monitored intraoperatively to ensure
that adequate levels of anesthesia were maintained. Supplemental anesthetics were given intramuscularly as needed
during the surgery. The area around the eye was draped in
an aseptic manner. A lid speculum was placed to retract
the lids. One drop of povidone–iodine 5.0% (Betadine) as
well as 1 drop of gatifloxacin were placed on the surface of
the eye just before the surgery began.
Using an aseptic technique and a surgical microscope, a
fornix-based conjunctival flap was fashioned. A corneoscleral incision was then made using a crescent blade, and the
anterior chamber was entered with a 3.0 mm keratome. A
capsulorhexis forceps was used to create a well-centered
continuous curvilinear capsulotomy (CCC) with a diameter
of approximately 5.0 mm; this was followed by hydrodissection. One milliliter of epinephrine 1:1000 and 0.5 mL of heparin (10 000 USP units/mL) were added to each 500 mL of
irrigation solution to facilitate pupil dilation and control
inflammation. The endocapsular technique was used with
the phacoemulsification performed entirely within the
capsular bag. The residual cortex was then removed with
the irrigation/aspiration (I/A) handpiece. An ophthalmic
viscosurgical device (OVD) (sodium hyaluronate 1.6%
[Amvisc Plus]) was used to expand the capsular bag, and
the IOLs were inserted into the capsular bag using the recommended injection system (Medicel Accuject 2.2). The
IOLs were loaded into the injector using an OVD (Physiovisc
Integral, Physiol S.A.). After the IOLs were injected, their position inside the capsular bag was noted in clock hours according to the position of the toric marks (the site where
the loops connect to the optic in the case of the nontoric
design). The OVD was removed using the phaco handpiece
primarily and then using the I/A handpiece. The wound was
closed with a 10-0 monofilament nylon suture.
Combination antibiotics and steroid ointment (neomycin polymyxin B sulfates dexamethasone) was applied
to the eyes following surgery. The same ointment was placed
in the eyes 4 times daily for the first postoperative week. It
was discontinued after 1 week. In the second postoperative
week, each animal received topical prednisolone acetate
eyedrops 4 times daily. It was discontinued after the second
week.
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Slitlamp Examination The eyes were evaluated grossly at
day 1. Slitlamp examination with scoring for ocular inflammatory response was performed 1, 2, 3, and 4 weeks postoperatively (G 2 days), and photographs were taken
as deemed necessary. At each examination, the rabbit
eyes were dilated using a combination of cyclopentolate
hydrochloride and phenylephrine hydrochloride solutions.
A standard scoring method in 11 specific categories was
used at each examination, including assessment of corneal
edema as well as the presence of cell and flare in the anterior chamber. The slitlamp scoring system used was
a modification of McDonald-Shadduck26 scoring. Retroillumination images with the pupil fully dilated were obtained
for photographic documentation of CCC size, anterior
capsule opacification (ACO), PCO, and any observed
capsule fibrosis.27,28 The position of the IOL optic–haptic
junction was followed with respect to the suture and noted
in clock hours at each examination to roughtly evaluate the
IOL rotation.
Gross Examination After the clinical examination at
4 weeks, the animals were anesthetized using a 1 to 2 cc intramuscular injection of a 7:1 mixture of ketamine hydrochloride and xylazine and then humanely killed with a 1 mL
intravenous injection of pentobarbital sodium/phenytoin
sodium. The globes were enucleated and placed in 10%
neutral buffered formalin for at least 24 hours. They were
then bisected coronally just anterior to the equator. Gross examination and photographs from the posterior aspect
(Miyake-Apple view) were performed to assess the ACO
and PCO development as well as the IOL fixation. The extent
and severity of ACO and PCO were scored on a scale from
0 (none) to 4 (severe).9,28
Gross photographs were taken using a camera
(model D40 with an AF Micro Nikkor 55 mm 1:2.8 lens,
Nikon Corp.) mounted on an MP4 Land camera
(Polaroid). They were analyzed with the BX40 microscope (Olympus Optical Co., Ltd.). Photomicrographs
were taken with a microscope digital camera (model
P20) mounted with a U-TV0.5C-3 C-mount video port
(Olympus Optical Co., Ltd.) attached to the light microscope for photodocumentation.
Histology After gross examination and photographs, all
globes were sectioned and the anterior segments including
the capsular bags were processed for standard light microscopy and stained with hematoxylin–eosin. Features such
as cell type, extent, and route of growth were documented
by serial photomicrographs.
Capsular Bag Size, Optic Decentration, Angle of Haptic–
Tissue Contact The methods for in vitro evaluation were
applied; however, the gross examination images were
used. The IOL optic diameter was used for scaling.
To enhance comprehension, results of a similar nature but
obtained by different test methods are presented and discussed together and treated as laboratory data.
Statistical Analysis
Descriptive statistics were used for all objective measurements with the mean and SD. For qualitative grading with
ordinal scales, the median is presented with the confidence
interval (CI). For paired tests, both parametric and nonparametric statistical analyses were performed. The conventional
way to perform analyses on paired data comprises the
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following 2 steps: (1) Determine whether the paired
differences are normally distributed via the KolmogorovSmirnov test. (2) If the Kolmogorov-Smirnov test is significant, indicating that the distribution of the differences is
not normal, a Wilcoxon (nonparametric test) paired test is
performed. If the Kolmogorov-Smirnov test is not significant, indicating that the distribution of the differences is
normal, a paired t test is performed.
Because there are fewer than 12 observations (as a general
rule), the results of the paired Wilcoxon nonparametric tests
of the collected data are presented.
The variability of the experimental laboratory results is
related to the method variability. All comparisons of laboratory measurement with simulated outcomes are purely
empirical, and statistical analyses were not performed.
The in silico results were obtained by finite element
simulation, based on the mean value obtained for the
elasticity (Young) modulus for both IOL materials.
Because no randomization is required for finite element
simulations, the outcomes are the same with any
given run. Therefore, statistical comparison is impossible.
The discrepancy between measured outcomes and simulated outcomes was evaluated for the sake of comparison
only.
RESULTS
Microscopic Observation In Vitro
Both IOLs were analyzed by confocal, optical, and
SEM, and the profiles were compared with the theoretical profiles. They both had sharp-edged optics posteriorly and anteriorly (Figure 3). Because they are
manufactured by a lathing/milling process, traces of
the manufacturing tool are seen peripherally
(Figure 3, A-II). The profiles observed by SEM
(Figure 3, BI-II) are identical to the theoretical profiles
(Figure 3, CI-II). A supplementary edge is designed at
the optic–haptic junction to further impede cellular
proliferation.
Elasticity Modulus In Vitro
The measured elasticity modulus of the 26% hydrophilic acrylic material (3.911 G 0.045 MPa) was lower
than that of the hydrophobic acrylic counterpart (5.829
G 0.036 MPa). A similar trend was seen for the constraints applied by the materials at 10% and 20% of
deformation, 0.342 G 0.005 MPa and 0.697 G 0.008
MPas for the hydrophilic material and 0.522 G 0.006
MPas and 1.164 G 0.010 MPas for the hydrophobic
material, respectively.
Radial Compression Force In Silico and In Vitro
Lower in silico or in vitro simulated capsular bag diameters induced higher radial compression forces
(Table 1). The radial compression forces simulated
numerically for the hydrophilic IOL were slightly
lower than those simulated for the hydrophobic IOL.
This is a direct consequence of the introduced Young
modulus values.
For the hydrophilic IOL, the radial compression
forces estimated in silico for a hypothetic capsular
bag diameter of 10.0 mm were comparable to those
obtained in vitro for both backed-up and free conditions. With the lower test diameter of 9.5 mm, the
values obtained in vitro were slightly lower than those
obtained in silico. For the hydrophobic IOL, the experimental results were systematically lower than the
Figure 3. Comparison of confocal (A) and SEM (B) results for the theoretical designs (C) of the hydrophilic IOL (series I) and hydrophobic IOL
(series II).
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Table 1. Axial shift and radial compression forces measured at in silico and in vitro conditions.
Radial Compression Force (mg)
Test Condition
In silico
Ø 10.0 mm backed up
Ø 10.0 mm free
Ø 9.5 mm backed up
Ø 9.5 mm free
In vitro
Ø 10.0 mm average
Ø 10.0 mm SD
Ø 9.5 mm average
Ø 9.5 mm SD
Axial Shift (mm)
Hydrophobic
Hydrophilic
Hydrophobic
Hydrophilic
157
165
252
249
105
111
169
171
d
0.073
d
0.122
d
0.073
d
0.122
72
7
117
9
88
46
100
21
0.029
0.016
0.061
0.013
0.089
0.013
0.110
0.014
Ø Z diameter
computer-generated results, with higher discrepancies
observed between the in vitro data and in silico data
(Table 1).
Vertical Compression Forces and Axial Shift In Silico
and In Vitro
Two parameters were measured on the axis vertical
to the IOL optic plane: the vertical compression force
applied by the optic and the optic axial shift. The first
parameter was determined in silico, and the second
was determined in silico and in vitro. As with the
radial compression forces, the hydrophobic acrylic
IOL in silico presented slightly higher vertical
compression than the hydrophilic acrylic IOL related
to the higher Young modulus introduced (Table 1).
Meanwhile, the numerically estimated axial shift
was the same for both IOLs. Experimentally, the hydrophobic IOL shifted less than the hydrophilic
IOL. This difference was statistically significant
(P value Z 0.0124 and .0004 at 10.0 mm and 9.5 mm
simulated capsular bag size, respectively; 2-tailed
paired t test). The vaulting angulation and the posterior capsular bag in vivo may be limiting factors in
terms of axial shift.
In in silico and in vitro conditions, a lower simulated
capsular bag size generally induced higher axial shift
no matter which IOL material was used.
For a 10.0 mm simulated capsular bag diameter, vertical compression forces of 26.8 mg and 18.0 mg were
calculated in silico for the hydrophobic IOL and the
hydrophilic IOL, respectively. Reducing the capsular
bag size to 9.5 mm resulted in a hypothetically
increased force of 38.5 mg and 25.9 mg, respectively.
Implantation Procedure in Rabbits
The injection of all IOLs was well controlled. In some
eyes, the IOL was fully injected in the capsular bag; in
other eyes, 1 of the trailing loops was injected out of the
bag but was easily placed in the bag with a hook. In rabbit 2, left eye (hydrophilic IOL), 1 trailing loop was
caught in the injector and torn. Because of this, it was
decided to include the extra rabbit, implanting the hydrophobic IOL in the right eye and the hydrophilic IOL
in the left eye. Rabbit 2 was kept throughout the followup period to study the effect of the broken loop on IOL
stability. The surgeon reported that a harder push was
generally necessary to implant the hydrophobic IOL
because of the higher Young modulus of the IOL material. At the end of the surgical procedure, the capsulorhexis was found to cover the optic periphery of the
IOLs for 360 degrees in all cases. The surgical incision
was located at 12 o’clock in all eyes, and all IOLs
were oriented with the major axis along the 6 o’clock
to 12 o’clock meridian.
Slitlamp Examination
At 1 day, corneal edema limited to the incision site
was generally found in all eyes, which were otherwise unremarkable. Signs of a postoperative inflammatory reaction were very mild in all eyes; a few
eyes in both groups had fibrin formation noted at
the 1-week examination, but it had almost
disappeared by the 2-week examination. Blood was
noted in the anterior segment in eye 6, right eye, at
the 1-week examination (likely from the incision
site), and a small amount was present in front of the
IOL at the end of the clinical follow-up. Starting at
the 2-week examination, many eyes in both groups
exhibited proliferative cortex material/pearls originating from the Soemmerring ring protruding anteriorly to the IOL; this began at the optic–haptic
junctions and caused synechiae in some cases. Soemmerring ring formation breached the capsular bend,
and LECs migrated behind the IOL.
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Figure 4. Slitlamp examination images at 4 weeks in rabbit 1. A: Right
eye (hydrophobic IOL). B: Left eye
(hydrophilic IOL).
Central PCO was absent at this point, but a
mild degree of PCO was observed at the 3-week
examination, increasing in intensity by the 4-week examination (generally beginning at the optic–haptic
junctions in both IOL groups) (Figure 4). No statistically significant difference was observed between the
groups, and the PCO scores at 4 weeks were as follows: hydrophobic IOL, 96.9% CI, 0.5-3.0; hydrophilic
IOL, 96.9% CI, 0.5-2.0 (P Z 1.000, Wilcoxon paired
test). A mild degree of ACO was observed in some
eyes in both IOL groups but was not statistically
significantly different between the 2 groups
(P Z .072, Wilcoxon paired test).
Both IOLs were well biotolerated with no statistically significant difference between groups in inflammatory deposits (P Z 1.000, Wilcoxon paired test),
limbal vascularization (P Z 1.000, Wilcoxon paired
test), iris vascularization (P Z .346, Wilcoxon paired
test), or posterior synechiae (P Z .850, Wilcoxon
paired test) (Figure 5). Zero levels of conjunctival injection, conjunctival discharge, corneal opacity, aqueous
flare, and IOL decentration were observed at the
same time point. The results for both IOLs showed
no statistically significant difference for the investigated parameters (Table 2). Flare was practically undetectable because signs of postoperative inflammatory
reaction were mild in all eyes, with fibrin formation
noted in a few eyes at the 1-week examination and in
none of the eyes at the 2-week examination.
Rough assessment of rotational stability throughout
the study showed no severe IOL rotation in either
group. The optic–haptic junctions remained at the
same positions relative to the sutures (expressed in
clock hours).
Figure 5. Slitlamp examination scores. The rectangles represent the 25th and 75th percentiles. The thick lines represent the median values. The
whiskers represent the maximum and minimum values excluding outliers. The open circles represent the outliers. Scale is from 0 (no) to 4 (severe). Total score refers to the sum (limbal vascularization C iris vascularization C posterior synechiae C inflammatory deposits C PCO C
ACO) for each animal (ACO Z anterior capsule opacification; PCO Z posterior capsule opacification).
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Table 2. Calculated rabbit capsular bag size and in vitro and in vivo optic decentration.
In Vivo Calculated
Rabbit Eye ID
Hydrophobic IOL
1 OD
2 OD
3 OD
4 OD
5 OD
6 OD
Mean
SD
Hydrophilic IOL
1 OD
2 OD
3 OD
4 OD
5 OD
6 OD
Mean
SD
In Vitro Optic Decentration
at ø 10.0 mm
In Vitro Optic Decentration
at ø 9.5 mm
Decentration
(%)
ø mm Rabbit
Capsule
Mean
SD
Mean
SD
2.33
3.83
3.50
2.67
1.83
1.33
2.58
0.96
9.57
9.35
10.03
9.83
9.59
9.68
9.68
0.23
1.38
d
d
d
d
d
d
d
1.09
d
d
d
d
d
d
d
1.02
d
d
d
d
d
d
d
1.16
d
d
d
d
d
d
d
2.33
5.33
4.33
4.67
3.67
2.67
3.83
1.17
9.6
9.61
9.86
9.78
9.44
9.07
9.55
0.31
1.31
d
d
d
d
d
d
d
0.77
d
d
d
d
d
d
d
1.44
d
d
d
d
d
d
d
0.67
d
d
d
d
d
d
d
ø Z diameter; IOL Z intraocular lens
Gross Examination
The scores for central PCO (P Z .93, Wilcoxon
paired test), peripheral PCO (P Z .93, Wilcoxon paired
test), and Soemmerring ring formation intensity (P Z
1.0, Wilcoxon paired test) multiplied by the Soemmerring ring area (P Z .34, Wilcoxon paired test) are
shown in Figure 6. Some PCO was observed centrally
and peripherally starting at the optic–haptic junctions
in 75% of cases, but the between-group difference was
not statistically significant (Figure 7). Mild degrees of
ACO (hydrophobic IOL: median Z 1 and 96.9% CI,
0.5-1.0; hydrophilic IOL: median Z 0.5 and 96.9% CI,
0-1) were also detected in both groups. No IOL tilt
and no IOL decentration were observed (including
rabbit 2, left eye, which had a broken loop). All IOLs
were fixated inside the capsular bag.
Soemmerring rings were observed mainly anteriorly or at the level of the haptics, suggesting posterior
lens/capsular bend formation as a result of the
5-degree angulation. The variation in capsulorhexis
coverage of the optic periphery was not statistically
significant given the standard variation rate (P Z
.93, Wilcoxon paired test) (hydrophobic IOL: 96.9%
CI, 60-280; hydrophilic IOL: 96.9% CI, 100-280). All
cross-correlation coefficients were lower than 0.05,
indicating no relationship or a poor relationship between capsulorhexis coverage and other parameters
(Figures 6 and 7).
Histopathologic Analysis
Representative microscopic images of the histopathologic investigation are shown in Figure 8. The histopathologic findings were similar in both IOLs, with
no significant difference between the right eyes and
left eyes. All rabbit eyes showed a moderate amount
of proliferative cortical material in the fornix forming
a Soemmerring ring. The material proliferating on
the anterior surface of the IOL varied from trace to a
large amount of material. In several rabbits, the anterior cortical material extended onto the pupillary
space, but there was no statistically significant difference between the groups. Similarly, based on a qualitative estimation, the posterior capsule proliferation
of cortical material ranged from trace to a moderate
amount with no statistically significant betweengroup difference. There was no sign of untoward
inflammation or toxicity in any rabbit eye (Figure 8).
Calculated Rabbit Capsular Bag
Table 2 shows
the results for these parameters. A rabbit capsular bag
diameter of 9.07 to 10.03 mm was calculated based on
the gross examination images obtained by the MiyakeApple technique. Based on the same images, the mean
optic decentration relative to the optic diameter was
calculated; it was 2.58% G 0.96% for the hydrophobic
In Vitro and In Vivo Optic Decentration (DX)
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Figure 6. Gross examination scores. The rectangles represent the 25th and 75th percentiles. The thick lines represent the median values. The whiskers represent the maximum and minimum values excluding outliers. The open circles represent the outliers. Scale is from 0 (no) to 4 (severe).
Total score refers to the sum (central PCO C peripheral PCO C SRI C Soemmerring ring area C ACO) for each animal. The capsulorhexis is
expressed as value 102 (ACO Z anterior capsule opacification; CR Z capsulorhexis; IOL Z intraocular lens; PCO Z posterior capsule opacification; SRA Z Soemmerring ring area; SRI Z Soemmerring ring intensity).
IOL and 3.83% G 1.17% for the hydrophilic IOL (P Z
.003, 2-tailed paired t test). These values are slightly
higher than those obtained with an in vitro model (P
! .001 at both 9.5 mm and 10.0 mm well diameters;
2-tailed paired t test). Given the SDs for the 2 conditions, this variation is not considered significant.
Moreover, it is close to the precision of the measurement technique. All these values are largely lower
than the tolerance limits acceptable by the current
ISO standard.
A degree of zero decentration was estimated by the
ophthalmologic examiner (L.W.) during clinical examination, suggesting unnoticeable decentration
levels.
The IOL that had 1 damaged trailing haptic (rabbit
2, left eye) presented with slightly higher calculated
optic decentration in vivo, but this remained clinically
unnoticeable (Table 2).
In Vitro and In Vivo Angle of Haptics Contact
To obtain comparable results, in vitro test well diameters of 9.5 mm and 10.0 mm were compared
with the measured in vivo rabbit capsular bag sizes
9.07 to 10.03 mm (Table 2). The tendency was for the
angle of haptic contact to increase as the test well
size or rabbit capsular bag size decreased (Figure 9).
The measured angle of haptic contact was the same
Figure 7. Gross postmortem examination images in rabbit 1. (A) Right
eye (hydrophobic IOL). (B) Left eye
(hydrophilic IOL).
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Figure 8. Images from histopathologic examinations (PCO Z posterior capsule opacification; Philic Z hydrophilic; Phobic Z hydrophobic).
for other similar conditions regardless of the IOL materials. The in vivo results were quite similar to the
measured in vitro results with the 9.5 mm test well
diameter, which is in line with the measured mean rabbit capsular bag size, 9.68 mm for the right eyes and
9.55 mm for the left eyes. The variations were relatively small for all conditions, 104 to 134 degrees of
capsule contact for the hydrophilic IOL and 104 to
129 degrees for the hydrophobic IOL (Figure 9).
DISCUSSION
The tested double-C-loop platform provides a symmetrical quadripod design with 2 by 2 oppositely
Figure 9. Angle of haptic contact measured under in vitro and
in vivo conditions (Ø Z diameter).
oriented haptics. This haptic orientation provides 4
contact points for fixation of the IOL in the capsular
bag. The IOL optic has a sharp edge, which limits
cellular migration at the posterior lens–capsule interface and prevents PCO formation.10 Hence, the obtained microscopic images of the edge corresponded
to the edge in the theoretical model.
The magnitude of the measured Young modulus is
considerably low and argues for good foldability of
both IOL materials during injection and good recovery
of shape and optical properties after injection.23
Very strong radial or vertical haptic compression
forces may induce capsule ovaling, stretch, or even
damage, while low radial compression forces may
result in poor IOL stability.23 These parameters
depend on the IOL material and design, capsular bag
size, and elasticity. Small capsule diameters, more
elastic materials, and nonflexible haptics may provoke
stronger compression forces in both directions. The
measured Young modulus is slightly higher for the hydrophobic acrylic material. The Young modulus was
used as a basic parameter for the numerical simulation
and, therefore, slightly higher compression forces
were estimated in silico for the hydrophobic IOL
than for the hydrophilic IOL.
The computer-simulated radial compression forces
were generally higher than those measured in vitro,
probably due to the absence of gravity as a parameter
in the in silico investigation. Another reason may be
the constant Young modulus considered in silico and
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the limit of elasticity. Meanwhile, partial drying of the
IOL during the period of the in vitro measurement
may change the elasticity. Moreover, finite element
simulation does not consider the relaxation processes
that occur in the IOL material on compression and is
based on purely elastic deformation. This explains
the difference between in silico and in vitro results
for the hydrophobic IOL, which is known to have significant plasticity.23 In contrast, the hydrophilic material is elastic and results, therefore, in similar in vitro
and in silico results.
Considering the large SD measured in vitro for the
radial compression force applied by the hydrophilic
IOL, the trend observed for the hydrophobic IOL can
be considered similar to that observed for the hydrophilic IOL. The same conclusion stands for the experimental axial shift results.
Although the difference between the axial shifts of
the 2 IOLs experimentally was statistically significant,
it is orders of magnitude lower than that measured for
the Envista MX60 (Bausch & Lomb), Acri.Tec 366D
(Carl Zeiss Meditec), and Sensar AR40E (Abbott Medical Optics) IOLs.23 This suggests that anteroposterior
stability of the IOL may be expected clinically,
ensuring the refractive stability of both IOLs in this
study (Podeye and Ankoris).
Higher radial than vertical compression forces obtained in silico for both IOLs suggest that capsular
bag size compensation at the plane parallel to the
IOL optic is better than compensation at the perpendicular plane. It can be explained by the ergonomic
design of the haptics, which provides relaxation
within the optic plane of the IOL. This improves the
ELP of the IOL for better refractive predictability. Rabbit histopathologic investigation demonstrated contact between the posterior optic surface and the
capsule. In the case of the hydrophobic acrylic IOL,
this may support the formation of the IOL–capsule
junction through physical or biological adhesion.
With the hydrophilic acrylic IOL, the posterior material–capsule contact is expected to impede cell migration and PCO formation.
The calculated rabbit capsular bag size postmortem was slightly lower than that reported in the scientific literature for this animal model.29 This may
be due to different factors such as the rabbit age,
weight, or the measuring technique used. Also, the
eyes had been fixated in formalin, and tissue
shrinkage likely occurred. This parameter was not
a subject of investigation in the present study and
was used only for comparative purposes. However,
the calculated value is comparable to typical human
capsular bag diameters29 and the results obtained
by this animal model are therefore an indication of
clinical behavior.
Low decentration levels were calculated in vitro and
in vivo. Moreover, they remained undetectable to the
ophthalmologic examiner (L.W.) and were rated as
zero decentration. This demonstrates the radial stability of the tested IOL design regardless of the material
and is in accord with the results from the radial and
vertical compression force measurements.
Both IOLs were well biotolerated, and no toxicity,
inflammation, or neovascularization was observed.
Given the reactivity of the rabbit model, it is difficult
to interpret the IOL material behavior in terms of
PCO, ACO, and Soemmerring ring formation.30 These
parameters are in direct relationship with protein
secretion and epithelial cell proliferation.31 Indeed,
some PCO was detected during the slitlamp examination and later on postmortem gross examination by the
Miyake-Apple technique. The PCO scores are comparable to those reported for other hydrophobic acrylic
IOLs.8,9 Because the tested hydrophobic acrylic IOL
is made of bioadhesive material,22 it is expected that
clinically, firm contact between the IOL and the posterior capsule will occur. Indeed, a clinical investigation
performed recently with this IOL confirmed this
expectation, and the results will be published soon.
The degree of haptic contact in vivo and in vitro (at
9.5 mm test well diameter) was similar relative to the
reproducibility and reliability of the results. More
than a 100-degree angle of contact was measured systematically, which suggests sufficient haptic–tissue
interface and friction. Indeed, a higher degree of haptic
contact is associated with stronger material/tissue
friction and would be beneficial in preventing the
IOL from rotating and misaligning. According to the
comparison of rabbit and human ocular parameters
presented in the literature,29 the human eye has a
slightly lower capsular bag diameter than the rabbit
eye. Therefore, it is suggested that in clinical cases,
the angle of haptic contact will be similar to or higher
than the values measured in the present study.
Although 1 haptic of 1 of the tested hydrophilic IOLs
(rabbit 2, left eye) was broken accidentally during implantation, the IOL remained centered in the eye. It is
assumed that even if a haptic were damaged accidentally, the remaining functional haptics would enable
the IOL to position as a conventional asymmetric
open-C-loop IOL. This intended micromechanical effect further enhances the IOL design safety, and the
present case is an indication for that.
In conclusion, this study is the first demonstration of
the reproducibility of data obtained in silico, in vitro,
and in vivo for a new double-C-loop symmetric platform manufactured in hydrophilic and hydrophobic
acrylic materials. Both IOLs were well biotolerated
and safe for patients, with no sign of toxicity or inflammation. Given the reactivity of the selected animal
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model, it is understandable that some PCO, ACO, and
Soemmerring rings were observed.
Both IOLs also demonstrated resilience to decentration as a result of sufficient contact and friction between the surrounding tissues and the IOL material.
Results suggest that the double-C-loop platform is a
suitable carrier of premium optics (multifocal and
toric) regardless of the IOL material.
WHAT WAS KNOWN
The material and design are known to be factors in the
postoperative behavior of an IOL. When inappropriately
selected, they might cause complications related to their
biomechanical stability and biocompatibility.
Premium (multifocal and toric) IOLs are sensitive to rotation, decentration, axial displacement, and PCO.
WHAT THIS PAPER ADDS
The double-C-loop symmetric quadripod platform naturally provided the IOL with axial and centration stability
regardless of the IOL material.
In combination with appropriately selected IOL material, it
is a suitable candidate for special optic IOLs.
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J CATARACT REFRACT SURG - VOL 41, JULY 2015
First author:
Dimitriya Bozukova, PhD
Physiol S.A., Liege, Belgium