Download Visual Outcomes and Safety of a Refractive Corneal Inlay

ORIGINAL ARTICLE
Visual Outcomes and Safety of a
Refractive Corneal Inlay for Presbyopia
Using Femtosecond Laser
Aliki N. Limnopoulou, MD, MSc; Dimitrios I. Bouzoukis, MD, FEBO; George D. Kymionis, MD, PhD;
Sophia I. Panagopoulou, PhD; Sotiris Plainis, PhD; Aristophanes I. Pallikaris, MSc;
Vladimir Feingold; Ioannis G. Pallikaris, MD, PhD
ABSTRACT
PURPOSE: To evaluate the outcomes and safety of a refractive inlay (Flexivue Micro-Lens, Presbia Coöperatief
U.A.) for the corneal compensation of presbyopia.
METHODS: This prospective, interventional clinical study
comprised 47 emmetropic presbyopes with a mean age
of 52⫾4 years (range: 45 to 60 years). The inlay was
inserted, centered on the line of sight, inside a corneal
pocket created in the patient’s nondominant eye, using
a femtosecond laser. Follow-up was 12 months. Visual
acuity, corneal topography, wavefront aberrometry, contrast sensitivity, structural corneal alterations, and questionnaires were evaluated.
RESULTS: Twelve months after surgery, uncorrected
near visual acuity was 20/32 or better in 75% of operated eyes, whereas mean uncorrected distance visual
acuity (UDVA) of operated eyes was statistically significantly decreased from 0.06⫾0.09 logMAR (20/20)
(range: ⫺0.08 to 0.26) preoperatively to 0.38⫾0.15
logMAR (20/50) (range: 0.12 to 0.8) (P⬍.001), and
mean binocular UDVA was not significantly altered
(P=.516). Seventeen patients lost one line of corrected
distance visual acuity in the operated eye. No patient
lost 2 lines in CDVA in the operated eye. Overall, higher
order aberrations increased and contrast sensitivity decreased in the operated eye. No tissue alterations were
found using corneal confocal microscopy. No intra- or
postoperative complications occurred.
CONCLUSIONS: Twelve months after implantation, the Flexivue Micro-Lens intracorneal refractive inlay seems to be an effective method for the
corneal compensation of presbyopia in emmetropic
presbyopes aged between 45 and 60 years old.
[J Refract Surg. 2013;29(1):12-18.]
D
uring the past decade in the field of refractive surgery there has been an increasing interest in the use
of corneal inlays for the treatment of presbyopia.
These may be implanted using flaps created by microkeratomes1,2 or femtosecond lasers,3,4 or pockets created by microkeratomes5,6 or femtosecond lasers.7 It is believed that inlays
have the advantage of being minimally invasive and easily
reversible.
In this study, we prospectively evaluated the efficacy and
safety of a refractive intrastromal inlay (Flexivue Micro-Lens;
Presbia Coöperatief U.A., Amsterdam, Netherlands) for the
corneal compensation of presbyopia, using a femtosecond
laser for creation of the pocket.
PATIENTS AND METHODS
This prospective, noncomparative, nonrandomized, interventional clinical study was performed at the Institute of
Vision and Optics, University Hospital of Crete, Greece.
Postoperative follow-up was scheduled at 1, 3, 6, 9, and 12
months. The study followed the tenets of the Declaration of
Helsinki and permission was obtained from the ethics committee of the University Hospital of Crete. After receiving a
detailed explanation of the study procedures, patient responsibilities, and possible complications, all patients signed informed consent.
REFRACTIVE CORNEAL INLAY
The Flexivue Micro-Lens is a transparent, hydrophilic concave-convex disc, manufactured from an optically clear copo-
From the Department of Ophthalmology, Vardinoyannion Eye Institute
of Crete (Limnopoulou, Bouzoukis, Kymionis, Panagopoulou, Plainis, A.I.
Pallikaris, I.G. Pallikaris), Crete, Greece; and Presbia Coöperatief U.A.,
Amsterdam, Netherlands (Feingold).
Supported by Presbia Coöperatief U.A. Medical Board.
doi:10.3928/1081597X-20121210-01
Drs. Pallikaris and Feingold are employed by and have received funding from
Presbia Coöperatief U.A. The remaining authors have no financial or proprietary interest in the materials presented herein.
Correspondence: Aliki N. Limnopoulou, MD, MSc, Institute of Vision and Optics
(IVO), University of Crete, Medical School, 71003 Heraklion, Crete, Greece.
Tel: 30 2810 371800; Fax: 30 2810 39465; E-mail: [email protected]
Received: May 7, 2012; Accepted: October 12, 2012
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Copyright © SLACK Incorporated
Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al
Figure 1. Flexivue Micro-Lens intracorneal inlay.
TABLE 1
Femtosecond-assisted
Pocket Laser Parameters
Femtosecond laser
iFS 150
Treatment type
inlay
Channel width (mm)
4.20
Channel offset (mm)
0.00
Channel depth (µm)
280
Channel spot separation
2
Channel line separation
2
Channel energy (µJ)
0.75
Side cut radius (mm)
4.50
Side cut angle (°)
30
Side cut spot separation (µm)/
Side cut layer separation (µm)
3/3
Side cut energy (µJ)
1.20
(iFS 150; Abbott Medical Optics, Santa Ana, California)
lymer of hydroxyethylmethacrylate and methylmethacrylate containing an ultraviolet blocker. The inlay has
a 3-mm diameter and a thickness of approximately 15
to 20 μm, depending on the additional power, which
acts by changing the refractive index of the cornea. The
lens material refractive index is 1.4583 and has a light
transmission ⬎95% at wavelengths above 410 nm. The
central 1.8-mm diameter of the disc is plano in power
and the peripheral zone has the appropriate addition
power. The available inlay refractive power ranges
from ⫹1.25 diopters (D) to ⫹3.50 D in 0.25-D increments. At the center of the disc, a 0.15-mm diameter
hole facilitates the transfer of oxygen and nutrients into
the cornea through the lens. Figure 1 depicts the design
of the Flexivue Micro-Lens inlay and Figure 2 shows a
representative patient after implantation.
During far vision, rays passing through the central
zone of the implant and the free peripheral corneal
tissue without the lens added refractive effect will be
Journal of Refractive Surgery • Vol. 29, No. 1, 2013
Figure 2. Patient 1 year after intracorneal inlay implantation showing
clarity of the cornea and absence of interference with slit-lamp examination of the anterior segments of the globe.
sharply focused on the retina, whereas rays that pass
through the refractive peripheral zone of the inlay will
be focused in front of the retina. During near vision,
rays passing through the central zone of the implant
will be out of focus behind the retina and rays passing
through the peripheral clear cornea will be blocked by
the pupil. The rays passing through the peripheral refractive zone of the inlay will be focused on the retina.
SURGICAL TECHNIQUE
The surgical procedure was performed under topical
anesthesia using proxymetacaine hydrochloride 0.5%
eye drops (Alcon Laboratories Inc, Ft Worth, Texas).
The intracorneal pocket was created using a femtosecond laser (IntraLase 150; Abbott Medical Optics,
Santa Ana, California). Using appropriate software, a
full lamellar cut was created at a depth of 280-μm with
a diameter of 9.00 mm and a line/spot separation of
2/2 μm. Table 1 shows the femtosecond laser parameters of the procedure. The tunnel was created from the
temporal incision cut to the center of the cornea corresponding to the visual axis. A special injector (Presbia
Coöperatief U.A.) was used to implant the inlay inside
the tunnel at the line of sight. To determine the line
of sight, the microscope and centration device of the
excimer laser (Allegretto Wave 400; WaveLight Technologie AG, Erlangen, Germany)8 were used.
Postoperatively, patients were treated with fluorometholone 0.1% (Falcon Pharmaceuticals, Ft Worth,
Texas) four times daily tapering over 1 week, along
with antibiotic drops (0.1% dexamethazone and 0.5%
chloramphenicol) and artificial tears.
PATIENT CRITERIA
Inclusion criteria were patients aged between 45 and
60 years with uncorrected near visual acuity (UNVA)
worse than 0.40 logMAR (20/50), uncorrected distance
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Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al
TABLE 2
Demographic Data
Demographic
Value (Mean⫾SD [Range])
No. of patients
47
Follow-up (mo)
12.6 (9 to 15)
Males/females
20/27
Right/left eyes
19/28
Age (y)
Implanted inlay (D)
51.55⫾4.11 (45 to 60)
2.48⫾0.22 (⫹1.75 to ⫹3.25)
UDVA (Snellen equivalent)
20/25 or better (20/25 to 20/16)
CDVA (Snellen equivalent)
20/20 or better (20/20 to 20/12)
Spherical equivalent
refraction (distance) (D)
0.66⫾0.35 (0.00 to ⫹1.25)
UNVA (Snellen equivalent)
20/50 or worse (20/50 to 20/80)
CNVA (Snellen equivalent)
20/25 or better (20/25 to 20/20)
Spherical equivalent
refraction (near) (D)
2.20⫾0.23 (1.75 to 2.90)
Corneal thickness (µm)
546.5⫾22.4 (508 to 599)
SD = standard deviation, UDVA = uncorrected distance visual acuity,
CDVA = corrected distance visual acuity, UNVA = uncorrected near visual
acuity, CNVA = corrected near visual acuity
visual acuity (UDVA) of 0.20 logMAR (20/32) or better
in either eye, and corrected near visual acuity (CNVA)
and corrected distance visual acuity (CDVA) of 0.10
logMAR (20/25) or better, respectively. Cycloplegic
sphere ranged between ⫺0.75 and ⫹0.75 diopters (D),
astigmatism ⬍1.00 D, and stable refraction (within
⫾0.50 D) for a 1-year period prior to implantation. All
patients wore reading glasses at least 1 year prior to
the preoperative evaluation. Central corneal pachymetry ⬎500 μm and endothelial cell density ⬎2000 cells/
mm2 on specular microscopy was necessary in the eye
to be operated.
Exclusion criteria were irregular astigmatism, pupil
diameter ⬍3 mm in photopic conditions, lens opacities that may affect vision, history of congenital or acquired anterior or posterior segment pathology or history of ocular surgery, and acute or chronic systemic
disease or any kind of immunosuppressive disorder.
CLINICAL EXAMINATION
A complete ophthalmic examination was performed
preoperatively and during each postoperative followup evaluation in all patients.
Visual Acuity Testing. Distance visual acuity was
tested using Early Diabetic Retinopathy Study (ETDRS)
logMAR charts (Precision Vision, La Salle, Illinois) at
4 m distance. Near visual acuity was tested at 33 cm
under a light source of 100 cd/m2 using the modified
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ETDRS chart for European wide use (Precision Vision).
All tests were performed monocularly and binocularly.
The dominant eye was determined using a card with a
central 1-inch hole test and confirmed with four dots
test, and a monovision trial was performed for at least
30 minutes, adding half of the add power for near in the
nondominant eye. Additionally, to evaluate the effect of
the inlay on distance vision, postoperative UDVA was
compared with preoperative distance visual acuity in
which a lens of equal refractive power with the lens that
was intended to be implanted was used.
The wavefront aberration function of the eye
was measured at scotopic condition with natural
(undilated) pupils using the WASCA COAS Wavefront
Analyzer (Carl Zeiss Meditec, Jena, Germany), which
is based on the Shack-Hartmann principle. Corneal
topography and corneal aberrations were measured
using the Topolyzer topographic system (Wavelight
Topolyzer, WaveLight Technologie AG). Aberration
coefficients, aligned to the pupil center, were analyzed
for 3- and 4-mm pupil diameters for the total eye, and
for 3- and 6-mm pupil diameters for the cornea.
Contrast sensitivity was measured using the
Functional Acuity Contrast Test (Stereo Optical Co
Inc, Chicago, Illinois) in photopic and mesopic conditions (with and without glare), binocularly, and monocularly. All measurements were performed in a room
without windows, with the lights on for measurement
under photopic conditions and off for measurement
under mesopic conditions and the door sealed. Photopic and mesopic conditions were standardized by the
machine at 200 lux for the photopic conditions and at
1 lux for the mesopic conditions.
Corneal structure was evaluated using confocal
microscopy with a modified confocal scanning laser
ophthalmoscope (HRT II; Heidelberg Engineering, Heidelberg, Germany). Images of the various layers of the
cornea were acquired at the optical center of the cornea and at the sites adjacent to or at the corneal inlay.
Quantitative analysis of endothelial cell density
was performed by counting cells from the confocal microscope. The automated counter was at a distant location, which was too far for every patient to attend to.
Other evaluation tests included tonometry (Goldmann
applanation tonometry) and central and peripheral ultrasound corneal pachymetry (50 MHz [Corneo-Gage
Plus; Sonogage Inc, Cleveland, Ohio]).
During the preoperative evaluation, a detailed discussion with each patient revealed his/her ideal distance of work, the amount of dependence on spectacles
for near vision, as well as his/her overall satisfaction
regarding vision throughout the day. Postoperatively,
patients were asked to complete a satisfaction questionCopyright © SLACK Incorporated
Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al
Figure 3. Accuracy of the intended additional power in diopters needed for corrected near visual acuity after inlay implantation.
Figure 4. Respective percentages of mean
uncorrected near visual acuity (logMAR) of
operated eyes in patients during follow-up.
naire for the evaluation of UNVA, UDVA, frequency of
eventual use of reading glasses, and for the presence or
absence of halos or glare.
STATISTICAL ANALYSIS
Statistical analysis was performed using SPSS 16.0
statistical package (SPSS Inc, Chicago, Illinois). All
values were monitored for normality with the Shapiro–
Wilks test and because their frequency distribution was
normal, variables were expressed as mean⫾standard
deviation. A P value ⬍.05 was considered statistically
significant. Paired Student t tests were performed to
compare mean values of the variables described.
Wavefront aberrations and contrast sensitivity were
evaluated with the Wilcoxon signed ranks test, because their frequency distributions were not normal.
RESULTS
Patient demographics are depicted in Table 2. All
patients attended scheduled 12-month postoperative
follow-up examinations.
VISUAL OUTCOMES
Accuracy. Figure 3 shows a histogram of the accuracy of attempted correction for near vision based on
postoperative add power. One year after treatment, additional power needed for CNVA was within ⫾0.50 D
in 99% of operated eyes.
Journal of Refractive Surgery • Vol. 29, No. 1, 2013
Efficacy and Stability. One year postoperatively,
mean UNVA significantly improved from 0.68⫾0.03 logMAR (20/100) (range: 0.40 to 1.00 [20/50 to 20/200]) to
0.14⫾0.09 logMAR (20/25) (range: ⫺0.02 to 0.36 [20/12
to 20/50]) (P⬍.001) in operated eyes, and from 0.53⫾0.13
logMAR (20/60) (range: 0.34 to 0.73 [20/40 to 20/100])
preoperatively to 0.13⫾0.13 logMAR (20/25) (range: 0.00
to 0.38 [20/20 to 20/50]) binocularly (P⬍.001). Figure 4
shows a histogram with the cumulative results for the
UNVA of the operated eyes achieved at each follow-up.
Uncorrected near visual acuity of the operated eyes was
20/32 or better in 75% of patients 12 months after inlay
implantation.
Mean UDVA in operated eyes significantly decreased from 0.06⫾0.09 logMAR (20/25) (range: ⫺0.08
to 0.26 [20/16 to 20/40]) preoperatively to 0.38⫾0.15
logMAR (20/50) (range: 0.12 to 0.8 [20/25 to 20/125])
(P⬍.001), whereas binocularly it did not change significantly (P=.516).
Mean UDVA of the operated eyes, achieved 1 year
after implantation, was compared to the mean preoperative CDVA of the same eyes, which were corrected
with a spherical lens power equal to the intended
power of the inlay. It was demonstrated that distance
vision was less influenced, as mean UDVA of the operated eyes was 0.38⫾0.15 logMAR (20/50) (range: 0.12
to 0.8), as opposed to 0.78⫾0.09 logMAR (20/125),
which would be expected (P⬍.001).
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Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al
At last follow-up, mean spherical equivalent refraction of the operated eyes changed significantly from
0.66⫾0.35 D (range: 0 to ⫺1.25 D) preoperatively to
⫺1.95⫾1.32 D (range: ⫺3.88⫾0.25 D) (P⬍.001). Mean
spherical equivalent refraction of the operated eyes
was not statistically significant during the postoperative period. Twelve months after implantation, mean
cylinder of the operated eyes was 0.72 D and was not
significantly different from preoperatively (⫺0.25 D)
(P=.07).
SAFETY AND COMPLICATIONS
At last follow-up, 37% (17) of patients had lost 1
line of CDVA (0.1 logMAR [20/25]) in the operated eye
with a statistically significant decrease from 0.00⫾0.05
logMAR (20/20) (range: ⫺0.08 to 0.18 [20/16 to 20/30])
preoperatively to 0.10⫾0.05 logMAR (20/25) (range:
⫺0.06 to 0.20 [20/16 to 20/32]), whereas no significant
decrease (P=.13) in CDVA was found binocularly. No
patient lost ⬎2 lines in CDVA in the operated eye. Corrected near visual acuity of operated eyes, as well as
binocularly, remained unchanged during follow-up
(P=.8).
Mean central corneal thickness of the operated
eyes did not change significantly after implantation
(546.5⫾22.4 μm preoperatively to 548.87⫾25.58
μm, P=.132). Change in mean intraocular pressure
of the operated eyes was not statistically significant
(P=.452).
No intra- or postoperative complications were demonstrated and no removal or replacement of any refractive intracorneal inlay was performed.
WAVEFRONT ANALYSIS, CONTRAST SENSITIVITY FUNCTION,
AND TOPOGRAPHY
The RMS of higher order ocular aberrations changed
from 0.33⫾0.14 to 0.79⫾0.17 μm (P⬍.001) at 3-mm
pupil diameter and from 0.52⫾0.20 to 1.15⫾0.29
μm (P⬍.001) at 4-mm pupil diameter 12 months after implantation. The RMS of spherical ocular aberration changed from 0.02⫾0.02 to 0.08⫾0.04 μm
(P=.001) at 3-mm pupil diameter and from 0.05⫾0.04
to 0.19⫾0.06 μm (P⬍.001) at 4-mm pupil diameter.
The Appendix (available as supplemental material in
the PDF version of this article) shows the changes in
all higher order aberration terms in RMS for the total eye at 3 and 4 mm preoperatively and 12 months
postoperatively.
The RMS of higher order corneal aberrations
changed from 0.14⫾0.05 to 0.22⫾0.08 μm (P=.003)
at 3-mm pupil diameter and from 0.34⫾0.10 to
0.55⫾0.20 μm (P⬍.001) at 6-mm pupil diameter. The
RMS of spherical corneal aberration changed from
16
0.03⫾0.03 to 0.09⫾0.07 μm (P=.008) at 3-mm pupil diameter and from 0.10⫾0.05 to 0.13⫾0.09 μm (P=1.00)
at 6-mm pupil diameter. The Appendix shows the
changes in all higher order aberration terms in RMS
for the cornea at 3 and 6 mm preoperatively and 12
months postoperatively.
Corneal topographic astigmatism was ⫺0.72⫾0.33 D
(range: ⫺0.12 to ⫺1.40 D) and changed to ⫺1.23⫾0.31
D (range: –0.70 to ⫺1.81 D) (P=.005). Mean surgically
induced astigmatism was ⫺0.44⫾0.19 D (range: ⫺0.18
to ⫺0.83 D) at mean axis of 169°⫾22°.
Change in contrast sensitivity of the operated eye
1 year postoperatively in mesopic conditions was
statistically significant at 1.5 cycles per degree (cpd)
(P=.009), 6 cpd (P=.012), and 12 cpd (P=.002), whereas
in photopic conditions it was statistically significant at
6 cpd (P=.007), 12 cpd (P⬍.001), and 18 cpd (P⬍.001).
Change in binocular contrast sensitivity in mesopic
conditions was significant only at 1.5 cpd (P=.049) and
in photopic conditions was not significantly different
at any frequency from the preoperative values.
ENDOTHELIAL CELL DENSITY AND CONFOCAL MICROSCOPY
Normal epithelial cells, subepithelial nerve plexus,
keratocyte scattering, and endothelial morphology
were observed in all patients at depths below and
above the inlay after 1 year.
Endothelial cell counts in the operated eyes were
not significantly changed (P=.776) 12 months after
surgery, from preoperative measurement of 2536⫾225
cells/mm2 to 2442⫾269.84 postoperatively (range:
2104 to 2899 cells/mm2).
PATIENT SATISFACTION QUESTIONNAIRE
During the preoperative evaluation, patients answered questions about their profession, everyday
needs, frequency of using a computer, and preferable
distance of working. These questions assisted the surgeon in deciding on the ideal inlay power for each patient. A general complaint about their inability to function without spectacles for near vision, annoyance for
constantly having to put them on and off, and satisfactory UDVA were noted.
Twelve months after implantation, 81.25% of patients perceived their UNVA in the operated eye as
excellent, whereas 93.75% were independent of their
near spectacles, with 6.25% of patients using spectacles for near tasks for less than half of everyday use. No
patient used spectacles for distance vision.
During the last follow-up, 81.25% of patients perceived their binocular UDVA as excellent compared to
53.33% at 1 month postoperatively, and 18.75% described it as good. As for UDVA of the operated eye, 1
Copyright © SLACK Incorporated
Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al
year after surgery, 18.75% of patients perceived it as
excellent and 81.25% as good.
One year after the procedure, 12.5% of patients still
experienced halos and 12.5% experienced glare.
DISCUSSION
In the present study, the outcomes of the use of a
refractive corneal inlay (Flexivue Micro-Lens) in emmetropic presbyopes were evaluated.
After implantation of the Flexivue Micro-Lens using
a femtosecond laser for creation of the pocket, mean
UNVA improved to 0.13 logMAR (20/25). Mean UDVA
of the operated eyes decreased to 0.38 logMAR (~20/50),
but this change was less than what would be expected if
compared to the distance visual acuity tested preoperatively using a lens with a refractive power equal to that
of the inlay. Corrected distance visual acuity decreased
in 37% of patients, but no inlay removal was required
as patients were satisfied with their binocular UNVA
and UDVA. The change in CDVA may be attributed to
the difficulty in performing manifest refraction over the
inlay, because of its two separate focal points. Other
types of corneal inlays have been used previously.1-7,9
The ACI-7000 (Acufocus Inc, Irvine, California) is a
small quasi-opaque inlay placed in the stromal bed after
creation of a conventional flap in the nondominant eye,
which increases the depth of focus by incorporating a
small central clear aperture 1.6 mm in diameter. Yilmaz
et al1 reported that after implantation of the ACI-7000
using a microkeratome, 85.3% of patients recorded
UNVA binocularly as J1 or better and Seyeddain et al3
reported that 2 years after implantation of the ACI-7000
using a femtosecond laser for the creation of the pocket,
96.9% of patients achieved J3 or better.
The PresbyLens (ReVision Optics Inc, Lake Forest,
California) is a different corneal inlay, which when
placed under a 120-μm flap, induces steepening of the
anterior curvature of the central cornea. Slade,8 who
presented 6-month results of PresbyLens inlay implantation in natural and postoperative refractive emmetropic presbyopes, reported mean UNVA of 20/25 and
no patient lost ⬎2 lines regarding distance vision.
The Invue lens (Biovision AG, Brugs, Switzerland)
is another corneal inlay implanted inside a corneal
pocket of the nondominant eye using a microkeratome.
Bouzoukis et al6 reported improved near visual acuity,
with 98% of patients achieving UNVA of 20/32.
In this study, total eye wavefront aberration analysis
showed a statistically significant increase in total higher
order aberrations as well as mean spherical aberration at
3- and 4-mm pupil diameter. Additionally, the RMS of
the spherical aberration of the cornea was increased at
3-mm pupil diameter. The corneal inlay has a plano 1.8Journal of Refractive Surgery • Vol. 29, No. 1, 2013
mm diameter in the center, whereas the annular peripheral zone (from 1.8 to 3.0 mm) has the add power creating a myopic effect. It is expected that both the corneal
and “total eye” higher order aberrations are influenced
by the implanted lens. A potential reason for the increase
in higher order aberrations is the decentration of the
inlay (in combination with its refractive periphery). In
practice, the surgeon attempts to align the inlay with the
coaxially sighted corneal reflex, but it remains unclear
whether another position would improve optical quality
with respect to centration of the corneal reflex. In any
case, an increase in the higher order aberrations in the
nondominant eye possibly further extends its depth of
focus. A similar increase was reported by Alió et al10 for
correcting hyperopia with intracorneal hydrogel inlays
after flap creation. Increased aberrations may influence
distance visual performance, but could also positively
contribute to near vision by increasing ocular depth of
focus. Charman11 noted the main requirement in presbyopia is an extended depth of focus to assure adequate
near and distance vision with good retinal contrast, rather
than achieving the highest level of acuity and modulation
transfer function at a single distance. As he suggested, an
increase in the depth of focus could be accomplished by
aiming at residual higher order aberrations. Similar increases were also reported for other inlays by Mulet et al2
using a corneal flap and Bouzoukis et al6 using a corneal
pocket created by a microkeratome.
The observed significant decrease in contrast sensitivity at high spatial frequencies (operated eyes) may
be attributed to induced aberrations.12,13
Mean central corneal thickness was not statistically significantly different after implantation. This
fact could be related either to the thinness of the inlay
(15 to 20 μm), which is even thinner than the standard deviation of the measurements, or to the sound
transmission change resulting in artifactual thickness
evaluation. However, as the central corneal thickness
and endothelial cell density were stable, along with
the confocal findings of healthy keratocytes, the procedure appears safe in early follow-up. No evidence
of biocompatibility problems was noted with this inlay. These results suggest that intrastromal inlay implantation may not lead to corneal thinning or corneal
melting within the first 12 months.
Patient satisfaction was high, as 81.25% of patients
perceived their UNVA as excellent 1 year after the procedure. Twelve months after implantation, 93.75% of
patients were independent of spectacles for all everyday near activity, compared to the fact that the majority
of patients were depending on spectacles for all near
activity prior to surgery. During the same time period,
81.25% of patients perceived their UDVA as excellent.
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Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al
The majority of patients reported the presence of
glare and halos from the first postoperative month,
which tended to become less intense during follow-up
and did not interfere with activities such as driving at
night. Homogeneity of the ocular structures affects retinal image quality. Light scattered from the edge of the
inlay spreads at larger angles over the retina and possibly contributes to the observed increase in glare and
halos. This would probably be more evident in cases
where the inlay is slightly tilted. It is not expected to
be remarkable when using a femtosecond laser to create the pocket, as was the case in our study.
The depth of the implantation was selected to be 280
μm, as the posterior stroma of the cornea has reduced
concentrations of keratocytes, which may improve tolerability of the inlay. Confocal images of the corneal
stroma did not reveal signs of instability. Larrea et al14
considered depth of implantation at 3/5 of the corneal
stroma, using computational methods, as optimal to facilitate nutrient flow and oxygen transport.
Patients with thinner corneas should be evaluated
after inlay implantation and a corneal pocket created
by a femtosecond laser may be able to expand the inclusion criteria. Femtosecond laser technology has
offered a new surgical approach in corneal refractive
surgery.15 The creation of femtosecond laser–assisted
pockets could improve the surgical procedure and increase the precision of the inlay position.
Possible limitations to our study include the length
of follow-up and the number of patients included. A
larger number of patients with a longer observation period is needed to confirm the stability and long-term
safety of the inlay implantation. Stereopsis evaluation
is another suggestion for future studies.
At 12 months postoperatively, implantation of the
Flexivue Micro-Lens in a femtosecond laser–created
pocket was a minimally invasive, effective surgical
treatment for presbyopes aged between 45 and 60
years.
AUTHOR CONTRIBUTIONS
Study concept and design (D.I.B., S.P., A.I.P., V.F., I.G.P.);
data collection (A.N.L., A.I.P.); analysis and interpretation of data
(A.N.L., D.I.B., G.D.K., S.I.P., A.I.P., V.F., I.G.P.); drafting of the manuscript (A.N.L.); critical revision of the manuscript (D.I.B., G.D.K.,
S.I.P., S.P., A.I.P., V.F., I.G.P.); statistical expertise (A.N.L., S.I.P.);
18
obtained funding (I.G.P.); administrative, technical, or material support (A.I.P.); supervision (D.I.B., V.F., I.G.P.)
REFERENCES
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de Pol C Intracorneal inlay for the surgical correction of presbyopia. J Cataract Refract Surg. 2008;34(11):1921-1927.
2. Mulet ME, Alio JL, Knorz MC. Hydrogel intracorneal inlays for
the correction of hyperopia: outcomes and complications after
5 years of follow-up. Ophthalmology. 2009;116(8):1455-1460.
3. Seyeddain O, Riha W, Hohensinn M, Nix G, Dexl AK, Grabner
G. Refractive surgical correction of presbyopia with the Acufocus small aperture corneal inlay: two-year follow-up. J Refract
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WM. Outcomes of PermaVision intracorneal implants for the
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5. Kymionis GD, Bouzoukis DI, Pallikaris IG. Corneal inlays: a
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Today Europe. 2007;3:48-50.
6. Bouzoukis DI, Kymionis GD, Panagopoulou SI, et al.Visual outcomes and safety of a small diameter intrastromal refractive inlay for the corneal compensation of presbyopia. J Refract Surg.
2012;28(3):168-173.
7. Bouzoukis DI, Kymionis GD, Limnopoulou AN, Kounis GA,
Pallikaris IG. Femtosecond laser-assisted corneal pocket creation using a mask for inlay implantation. J Refract Surg.
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2006;113(10):1807-1812.
13. Kymionis GD, Yoo SH, Ide T, Culbertson WW. Femtosecondassisted astigmatic keratotomy for post keratoplasty irregular
astigmatism. J Cataract Refract Surg. 2009;35(1):11-13.
14. Larrea X, De Courten C, Feingold V, Burger J, Büchler P. Oxygen and glucose distribution after intracorneal lens implantation. Optom Vis Sci. 2007;84(12):1074-1081.
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Copyright © SLACK Incorporated
APPENDIX
Higher Order Aberrations Preoperatively and 12 Months Postoperatively
Root-Mean-Square (µm)
Zernike RMS
Z-33
Z-13
Z31
Z33
Z-44
Z-24
Z40
Z42
Z44
HOAs
Total Eye
Pupil Diameter
(mm)
Preop
Postop
3
0.03⫾0.02
0.05⫾0.03
4
0.07⫾0.05
3
0.02⫾0.02
4
3
Corneal
Pupil Diameter
(mm)
Preop
Postop
P Value
.381
3
0.05⫾0.04
0.08⫾0.09
1.000
0.09⫾0.06
.113
6
0.09⫾0.07
0.35⫾0.23
⬍.001
0.06⫾0.04
.005
3
0.04⫾0.03
0.07⫾0.05
.213
0.05⫾0.03
0.11⫾0.07
.002
6
0.12⫾0.09
0.14⫾0.10
1.000
0.03⫾0.03
0.14⫾0.10
.001
3
0.04⫾0.03
0.05⫾0.04
1.000
4
0.06⫾0.06
0.29⫾0.13
⬍.001
6
0.12⫾0.10
0.11⫾0.08
1.000
3
0.02⫾0.02
0.05⫾0.04
.001
3
0.06⫾0.04
0.07⫾0.06
1.000
4
0.04⫾0.03
0.12⫾0.09
.001
6
0.16⫾0.12
0.17⫾0.13
1.000
P Value
3
0.01⫾0.01
0.01⫾0.01
.055
3
0.03⫾0.02
0.04⫾0.03
.787
4
0.02⫾0.02
0.04⫾0.02
.003
6
0.05⫾0.04
0.07⫾0.06
1.000
3
0.01⫾0.003
0.03⫾0.02
.001
3
0.02⫾0.01
0.02⫾0.02
1.000
4
0.01⫾0.01
0.03⫾0.02
.007
6
0.03⫾0.03
0.03⫾0.03
1.000
3
0.02⫾0.02
0.08⫾0.04
.001
3
0.03⫾0.03
0.09⫾0.07
.008
4
0.05⫾0.04
0.19⫾0.06
⬍.001
6
0.10⫾0.05
0.13⫾0.09
1.000
3
0.01⫾0.01
0.04⫾0.04
.004
3
0.03⫾0.05
0.04⫾0.03
1.000
4
0.02⫾0.02
0.03⫾0.03
.356
6
0.05⫾0.04
0.04⫾0.04
1.000
3
0.01⫾0.006
0.02⫾0.01
.068
3
0.04⫾0.03
0.06⫾0.04
.548
4
0.02⫾0.01
0.05⫾0.03
.006
6
0.04⫾0.04
0.17⫾0.11
⬍.001
3
0.33⫾0.14
0.79⫾0.17
⬍.001
3
0.14⫾0.05
0.22⫾0.08
.003
4
0.52⫾0.20
1.15⫾0.29
⬍.001
6
0.34⫾0.10
0.55⫾0.20
⬍.001
RMS = root-mean-square, HOAs = higher order aberrations