Download Femtosecond Laser versus Mechanical Microkeratome for LASIK

Femtosecond Laser versus Mechanical
Microkeratome for LASIK
A Randomized Controlled Study
Sanjay V. Patel, MD,1 Leo J. Maguire, MD,1 Jay W. McLaren, PhD,1 David O. Hodge, MS,2
William M. Bourne, MD1
Purpose: To compare corneal haze (backscattered light) and visual outcomes between fellow eyes randomized to LASIK with the flap created by a femtosecond laser (bladeless) or with the flap created by a mechanical
microkeratome.
Design: Randomized, controlled, paired-eye study.
Participants: Twenty-one patients (42 eyes) received LASIK for myopia or myopic astigmatism.
Methods: One eye of each patient was randomized to flap creation with a femtosecond laser (IntraLase FS,
IntraLase Corp., Irvine, CA) with intended thickness of 120 ␮m, and the fellow eye to flap creation with a
mechanical microkeratome (Hansatome, Bausch & Lomb, Rochester, NY) with intended thickness of 180 ␮m.
Patients were examined before and at 1, 3, and 6 months after LASIK.
Main Outcome Measures: Corneal backscatter, high-contrast visual acuity, manifest refractive error, contrast sensitivity, and intraocular forward light scatter were measured at each examination. Flap thickness was
measured by confocal microscopy at 1 month, and patients were asked if they preferred the vision in either eye
at 3 months.
Results: Corneal backscatter was 6% higher after bladeless LASIK than after LASIK with the mechanical
microkeratome at 1 month (P ⫽ 0.007), but not at 3 or 6 months. High-contrast visual acuity, contrast sensitivity,
and forward light scatter did not differ between treatments at any examination. Flap thicknesses at 1 month were
143⫾16 ␮m (bladeless, mean ⫾ standard deviation) and 138⫾22 ␮m (mechanical microkeratome), with no
statistical difference in variances. At 3 months, 5 patients preferred the bladeless eye, 7 patients preferred the
microkeratome eye, and 9 patients had no preference.
Conclusions: The method of flap creation did not affect visual outcomes during the first 6 months after
LASIK. Although corneal backscatter was greater early after bladeless LASIK than LASIK with the mechanical
microkeratome, patients did not perceive a difference in vision. Ophthalmology 2007;114:1482–1490 © 2007 by
the American Academy of Ophthalmology.
Excimer laser refractive surgery is currently the most common surgical procedure performed on the central cornea.
LASIK involves photoablation of corneal stroma deep to an
anterior corneal flap. Flaps have traditionally been created
with mechanical microkeratomes, but more recently, femOriginally received: July 28, 2006.
Accepted: October 22, 2006.
Manuscript no. 2006-837.
1
Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota.
2
Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
Presented at: Association for Research in Vision and Ophthalmology
Annual Meeting, May 2006, Fort Lauderdale, Florida.
Supported by the National Institutes of Health, Bethesda, Maryland (grant
no. EY 02037); Research to Prevent Blindness, Inc., New York, New York;
and Mayo Foundation, Rochester, Minnesota.
The authors have no commercial or proprietary interest in the products or
companies mentioned in the article.
Correspondence to Sanjay V. Patel, MD, 200 First Street SW, Rochester,
MN 55905. E-mail: [email protected].
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© 2007 by the American Academy of Ophthalmology
Published by Elsevier Inc.
tosecond laser technology has emerged as an alternative for
flap creation.1 Femtosecond lasers are ultrafast lasers that
precisely photodisrupt tissue by using very short duration
energy pulses. The low amount of energy imparted to the
tissue minimizes collateral tissue damage in theory.2,3 The
precision of femtosecond lasers may make this technology
safer than mechanical microkeratomes with more predictable flap parameters.1
Corneal haze after refractive surgery is typically associated with surface photoablation4 and rarely with LASIK.5
Our clinical and confocal microscopy6 observations suggest
that corneas treated with the femtosecond laser may exhibit
more haze after LASIK compared with corneas treated with
mechanical microkeratomes. Haze, or increased corneal
backscatter, may result from the greater inflammatory response associated with femtosecond laser flap creation,7,8
and can be measured objectively and noninvasively.9 Previous studies comparing the 2 methods of flap creation have
reported similar visual acuity outcomes in the short-term
after LASIK, and emphasize more predictable flap paramISSN 0161-6420/07/$–see front matter
doi:10.1016/j.ophtha.2006.10.057
Patel et al 䡠 Femtosecond Laser versus Mechanical Microkeratome
eters with the femtosecond laser.10 –12 In the present study,
which was not sponsored by any manufacturer, 1 eye of
each patient was randomized to LASIK with the flap created
by a femtosecond laser (“bladeless LASIK”), and the fellow
eye received LASIK with the flap created by a mechanical
microkeratome. We objectively measured changes in corneal backscatter, visual function, and variability of flap
thickness, and we report the results from the first 6 months
of this paired-eye study.
Materials and Methods
Subjects
Twenty-one subjects were recruited from patients attending the
refractive surgery service at Mayo Clinic College of Medicine. All
patients had myopia or myopic astigmatism, were ⱖ21 years old,
and were determined to be suitable candidates for LASIK after a
rigorous screening examination. Subjects were excluded if they
had any corneal abnormalities; a history of ocular disease, trauma,
or surgery; diabetes mellitus or other systemic disease known to
affect the eye; or if they used ocular medications. Systemic medications were permitted unless they were known to affect the
cornea or anterior segment. Mean subject age at surgery was
38⫾10 years (mean ⫾ standard deviation; range, 22–54 years).
This study complied with the Health Insurance Portability and
Accountability Act and was approved by our Institutional Review
Board. Informed consent was obtained from all subjects after
explanation of the nature and possible consequences of the study.
Randomization
Patients were stratified by ocular dominance and then 1 eye of each
patient was randomized to LASIK with the flap created by a
femtosecond laser, and the other eye to LASIK with the flap
created by a mechanical microkeratome. Ocular dominance was
tested by asking patients to use both hands to frame a distant target
while an observer determined with which eye the target was
aligned.
LASIK Procedure
Bladeless flaps were created with a 15-kHz femtosecond laser
(IntraLase FS, IntraLase Corp., Irvine, CA). All flaps had a superior hinge and intended thickness of 120 ␮m. Raster line and spot
separation were 9 and 11 ␮m, respectively; raster energy was 2.3
␮J, and side-cut energy was 2.5 ␮J. Flaps created by the mechanical microkeratome (Hansatome, Bausch & Lomb, Rochester, NY)
had a superior hinge with intended thickness of 180 ␮m. Ablation
of the stromal bed was performed with a VISX Star S4 excimer
laser (VISX, Santa Ana, CA) with radiant exposure of 160 mJ/cm2.
Emmetropia was attempted in all cases by using an ablation zone
that ranged from 6.5⫻6.5 mm for spherical corrections to 6.5⫻5.0
mm for astigmatic corrections.
Both eyes of each patient were treated by 1 of the study
ophthalmologists (SVP, LJM, or WMB) on the same day. All
procedures followed a standard protocol: the bladeless flap was
created first on the eye randomized to the femtosecond laser; the
fellow eye then received a full LASIK procedure with the flap
created by the mechanical microkeratome; finally, LASIK was
completed on the first eye by separating and lifting the flap created
by the femtosecond laser and ablating the stroma. It was not
possible to mask patients as to which treatment was received in
each eye. Postoperative topical medication regimens were identical
for each eye and consisted of ciprofloxacin ophthalmic solution 4
times per day for 5 days, and fluorometholone 0.1% 4 to 8 times
daily with a taper over 3 weeks.
Outcome Measures
Patients were examined before LASIK and at 1, 3, and 6 months
after surgery. At each examination, high-contrast visual acuity,
manifest refraction, contrast sensitivity, intraocular forward light
scatter, and corneal backscatter were measured by observers
masked as to which treatment was received in each eye. Corneas
were also examined by confocal microscopy in vivo.
High-contrast visual acuity was measured by using the electronic Early Treatment of Diabetic Retinopathy Study testing
protocol.13 Uncorrected visual acuity (UCVA) and best-spectacle
corrected visual acuity (BSCVA) were recorded as letter scores,
which were converted to logarithm of the minimum angle of
resolution (logMAR).13
Contrast sensitivity was examined by using the Functional
Acuity Contrast Test (Stereo Optical, Inc., Chicago, IL)14 with
best-spectacle correction in place. Patients were asked the orientation of lines of decreasing contrast for 5 spatial frequencies
(1.5, 3, 6, 12, and 18 cycles/degree) under mesopic illumination
(6 cd/m2).
Intraocular forward light scatter was measured with a stray
light meter,15 which used the direct compensation method to
measure retinal stray light.16 This instrument measured the effect
on central vision of light scattered within the eye from incident
light sources at angles of 3.5, 10, and 28 degrees from the visual
axis. A “stray light parameter” was defined as log(␾2 L/E), where
␾ was the angle between the optical axis and the ring of modulated
lights, L was the luminance of the compensating light at the center
of the field, and E was the illuminance on the subject’s eye caused
by the ring of lights.16 The stray light parameter was affected by
scatter from all optical components of the eye, including all aberrations that degrade the point-spread function. Forward light scatter was proportional to the stray light parameter.
Central corneal backscatter (haze) was measured by using a
custom scatterometer.9,17 Briefly, a modified slit-lamp was used to
acquire high-magnification images of a narrow slit-beam through
the cornea. Backscattered light from the anterior, middle, and
posterior thirds of the cornea was measured from the intensity
across the digitized image of the cornea. All measurements were
standardized to a reference and expressed in scatter units.9 Although corneal haze consists of backscatter and reflectance,18 we
will use the term backscatter broadly to include reflectance.
Confocal microscopy in vivo was performed with the ConfoScan 3 or ConfoScan 4 confocal microscopes (Nidek Technologies, Greensboro, NC), and with the Tandem Scanning confocal
microscope (Tandem Scanning Corporation, Reston, VA). Images
were acquired by continuous through-focusing as described in
detail previously.19,20 Qualitative assessments of keratocytes were
made from images acquired by the ConfoScan confocal microscopes. Flap thickness at 1 month was calculated from the Tandem
Scanning confocal microscope images by measuring the distance
between the surface epithelium and the interface peak or image.21
Data Analysis
The study was powered to detect a difference of 1 standard
deviation in corneal haze between eyes (i.e., treatments), and this
required a minimum of 13 subjects. Differences between treatments at each examination, and differences between preoperative
and postoperative examinations for each treatment, were assessed
by using 2-tailed paired t tests if the data were distributed normally
and Wilcoxon signed-rank tests if they were not. Differences
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Ophthalmology Volume 114, Number 8, August 2007
Figure 1. Corneal backscatter before and after LASIK. Backscatter in the anterior, middle, and posterior thirds of the cornea was compared between
treatments at each examination, and P values were adjusted for 4 comparisons by the Bonferroni technique. Backscatter in the middle third of the cornea
was higher 1 month after bladeless LASIK compared with LASIK with the mechanical microkeratome. Backscatter was measured in scatter units (SU),8
and depth of cornea was expressed as a percentage from anterior to posterior.
between treatments at the 4 examinations were adjusted for 4
comparisons, and differences between the 3 postoperative examinations compared to preoperative within each treatment were adjusted for 3 comparisons. P⬍0.05 was considered statistically
significant. All statistical analyses were performed with Statistical
Analysis System Version 9.1.3 (SAS Institute Inc., Cary, NC).
Minimum detectable differences were calculated for nonsignificant differences assuming that there were 21 independent
observations (␣ ⫽ 0.05/3 or 0.05/4 depending on the comparison,
ß ⫽ 0.20). Correlations were assessed by using Pearson’s correlation coefficient if the data were distributed normally and Spearman’s test if they were not.
At the 3-month study visit, subjects were asked if they preferred the vision in one eye or the other, or whether they had no
preference. We selected the 3-month visit because visual acuity
and manifest refraction should have been stable with minimal
influence from ocular surface pathology.
Results
Corneal Backscatter
Before LASIK, peak corneal backscatter originated from the anterior corneal surface, and a smaller peak was usually associated
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with the posterior surface (Fig 1). There were no differences in
backscatter from the anterior, middle, or posterior thirds of the
cornea between fellow eyes before surgery (Fig 1, Table 1).
Backscatter from the middle third of the cornea was 6% higher
at 1 month after bladeless LASIK compared to LASIK with the
mechanical microkeratome (P ⫽ 0.007). No differences in backscatter were detected at 3 or 6 months (Fig 1, Table 1). Backscatter
was higher in the anterior and middle thirds of the cornea at 1 and
3 months after bladeless LASIK compared with before surgery
(Pⱕ0.001), and was higher in the anterior third of the cornea at 1
month after LASIK with the microkeratome compared to before
surgery (P ⫽ 0.04).
Confocal microscopy qualitatively showed more activated keratocytes in images centered at the interface early after bladeless
LASIK than after LASIK with the microkeratome (Fig 2).
High-Contrast Visual Acuity and Refractive Error
No differences were detected in high-contrast UCVA and BSCVA
between eyes that received a bladeless flap or eyes that received a
microkeratome flap at any examination through 6 months after
LASIK (Table 2). The minimum detectable differences in postoperative UCVA and BSCVA were ⱕ 0.11 logMAR and ⱕ 0.07
logMAR, respectively, during the first 6 months after surgery.
Best-spectacle corrected visual acuity did not change at any ex-
Patel et al 䡠 Femtosecond Laser versus Mechanical Microkeratome
Table 1. Corneal Backscatter
Corneal Backscatter (Scatter Units), n ⴝ 21
Depth of Cornea Treatment
Anterior third
Femtosecond laser
Mechanical microkeratome
P (MDD)
Middle third
Femtosecond laser
Mechanical microkeratome
P (MDD)
Posterior third
Femtosecond laser
Mechanical microkeratome
P (MDD)
Preoperative
1 Month
3 Months
6 Months
451⫾38
457⫾35
0.70 (18)
506⫾65*
496⫾64‡
⬎0.99 (37)
499⫾76†
481⫾58
0.25 (33)
464⫾56
463⫾45
⬎0.99 (28)
275⫾27
277⫾27
⬎0.99 (14)
304⫾33†
287⫾24
0.007
302⫾31*
292⫾29
0.07 (15)
288⫾28
291⫾43
⬎0.99 (26)
242⫾23
246⫾28
⬎0.99 (17)
241⫾24
243⫾24
⬎0.99 (12)
246⫾20
246⫾16
⬎0.99 (12)
242⫾22
245⫾23
⬎0.99 (10)
MDD ⫽ minimum detectable difference (paired data, ␣ ⫽ 0.05/4, ß ⫽ 0.20, n ⫽ 21).
Data are presented as mean values ⫾ standard deviation. P values comparing treatments were adjusted for 4
comparisons by the Bonferroni technique.
*P⬍0.001; †P ⫽ 0.001; ‡P ⫽ 0.04 versus preoperative (after adjusting for 3 comparisons by the Bonferroni technique).
amination after surgery compared with before surgery for either
treatment (Table 2). At 6 months after bladeless LASIK, BSCVA
increased by ⱖ 0.1 logMAR in 1 eye and decreased by ⱖ 0.1
logMAR in 4 eyes. At 6 months after LASIK with the microkeratome, BSCVA did not increase by ⱖ 0.1 logMAR in any eye, and
decreased by ⱖ 0.1 logMAR in 4 eyes. No eye lost ⱖ 0.2 logMAR
after either treatment.
For both treatments at all postoperative examinations, there was
no correlation between BSCVA and corneal backscatter. Manifest
refractive error did not differ between treatments before or after
LASIK (Tables 3, 4).
Contrast Sensitivity
Contrast sensitivity did not differ between treatments preoperatively or at any postoperative examination for any spatial frequency (Fig 3). At the highest spatial frequency (18 cycles/
degree), contrast sensitivity increased at 3 months after LASIK
Figure 2. Confocal microscopy images (ConfoScan, Nidek Technologies) of both corneas of 1 subject before and after LASIK. The right eye was
randomized to bladeless LASIK, and the left eye to LASIK with the mechanical microkeratome. Preoperative images are from a depth equivalent to the
postoperative interface and show normal keratocyte nuclei. Postoperative images are centered at the interface and qualitatively show more keratocyte
activation, manifest as visible cell bodies and processes, with bladeless LASIK at 1 month. At 3 months, keratocyte activation appears to diminish in this
patient and is similar between treatments. Uncorrected Snellen visual acuity was 20/15 in each eye at both 1 and 3 months.
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Ophthalmology Volume 114, Number 8, August 2007
Table 2. Visual Acuity (VA)
VA (logMAR), n ⴝ 21 (Snellen Equivalent)
Treatment
Preoperative
Uncorrected VA
Femtosecond laser
Mechanical microkeratome
P (MDD)
Best spectacle corrected VA
Femtosecond laser
Mechanical microkeratome
P (MDD)
1 Month
0.93⫾0.33 (20/160)
0.98⫾0.35 (20/200)
0.45 (0.10)
⫺0.07⫾0.07 (20/15)
⫺0.08⫾0.05 (20/15)
0.67 (0.04)
3 Months
6 Months
0⫾0.13 (20/20)
0.01⫾0.14 (20/20)
⬎0.99 (0.11)
⫺0.01⫾0.14 (20/20)
⫺0.01⫾0.12 (20/20)
⬎0.99 (0.08)
0.01⫾0.11 (20/20)
⫺0.02⫾0.12 (20/20)
0.71 (0.07)
⫺0.05⫾0.09 (20/15)
⫺0.05⫾0.08 (20/15)
⬎0.99 (0.05)
⫺0.07⫾0.09 (20/15)
⫺0.07⫾0.09 (20/15)
⬎0.99 (0.07)
⫺0.06⫾0.09 (20/15)
⫺0.06⫾0.09 (20/15)
⬎0.99 (0.05)
MDD ⫽ minimum detectable difference (paired data, ␣ ⫽ 0.05/4, ß ⫽ 0.20, n ⫽ 21).
Data are presented as mean values ⫾ standard deviation. P values comparing treatments were adjusted for 4 comparisons by the Bonferroni technique.
For both methods of flap creation, best spectacle-corrected VA did not change after LASIK versus preoperative.
(bladeless, P ⫽ 0.02; mechanical microkeratome, P⬍0.001), but
no difference was detected at 6 months for either treatment.
Intraocular Forward Light Scatter
Forward light scatter within the whole eye did not differ between
treatments at any examination (Table 5). Forward light scatter
from stray light incident at 10 degrees was higher than preoperative at 6 months after LASIK with the mechanical microkeratome
(P ⫽ 0.04) but not after bladeless LASIK (minimum detectable
difference ⫽ 0.17, ␣ ⫽ 0.05/3, ß ⫽ 0.20).
For both treatments at all postoperative examinations, there
were no significant correlations between intraocular forward light
scatter and corneal backscatter or between intraocular forward
light scatter and contrast sensitivity.
Flap Thickness
One month after bladeless LASIK, flap thickness was 143⫾16 ␮m
(range, 110 –172 ␮m), thicker than the intended 120 ␮m
(P⬍0.001). One month after LASIK with the mechanical microkeratome, flap thickness was 138⫾22 ␮m (range, 96 –181 ␮m),
thinner than the intended 180 ␮m (P⬍0.001). The ratio of variances was 1.86 (P ⫽ 0.18, Pitman test for paired data), and the
minimum detectable ratio of variances was 3.44 (␣ ⫽ 0.05, ß ⫽
0.20, n ⫽ 21).
Patient Preference
At 3 months after LASIK, 5 patients preferred the vision in the eye
that received the bladeless flap, 7 patients preferred the vision in
the eye that received the mechanical microkeratome flap, and 9
patients expressed no preference. For the 12 patients who did
express a preference, the preferred eye was the dominant eye in 5
cases, and was the eye with better UCVA (ⱖ0.1 logMAR) in 4
cases.
Discussion
This prospective study, in which fellow eyes were randomized to LASIK with flaps created by a femtosecond laser
and by a mechanical microkeratome, showed no clinical or
statistical differences in high-contrast visual acuity, manifest refractive error, contrast sensitivity, or intraocular forward light scatter through 6 months after surgery.
Corneal backscatter increased with both treatments during the first month after LASIK, but was 6% higher in the
corneas treated with the femtosecond laser than in corneas
treated with the mechanical microkeratome. Increased backscatter with bladeless LASIK may be the result of increased
inflammation compared with LASIK with mechanical mi-
Table 3. Manifest Refractive Error
Refractive Error (D), n ⴝ 21
Treatment
Manifest sphere
Femtosecond laser
Mechanical microkeratome
P (MDD)
Manifest cylinder
Femtosecond laser
Mechanical microkeratome
P (MDD)
Preoperative
1 Month
3 Months
6 Months
⫺4.02⫾1.61
⫺4.15⫾1.62
⬎0.99 (0.35)
⫺0.15⫾0.27
⫺0.21⫾0.31
⬎0.99 (0.15)
⫺0.21⫾0.25
⫺0.29⫾0.33
⬎0.99 (0.18)
⫺0.33⫾0.33
⫺0.30⫾0.27
⬎0.99 (0.12)
0.70⫾0.82
0.77⫾0.88
⬎0.99 (0.27)
0.13⫾0.26
0.08⫾0.20
⬎0.99 (0.12)
0.13⫾0.26
0.10⫾0.23
⬎0.99 (0.09)
0.20⫾0.27
0.15⫾0.23
⬎0.99 (0.12)
MDD ⫽ minimum detectable difference (paired data, ␣ ⫽ 0.05/4, ß ⫽ 0.20, n ⫽ 21).
Data are presented as mean values ⫾ standard deviation. P values comparing treatments were adjusted for 4
comparisons by the Bonferroni technique.
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Patel et al 䡠 Femtosecond Laser versus Mechanical Microkeratome
Table 4. Postoperative Manifest Sphere and Cylinder, n (%)
Difference from
Emmetropia
1 Month
FL
MM
3 Months
FL
MM
6 Months
FL
MM
Manifest sphere
⬍0.5D
20 (95) 18 (86) 19 (90) 17 (81) 19 (90) 19 (90)
ⱖ0.5D
1 (5)
3 (14) 2 (10) 4 (19) 2 (10) 2 (10)
Manifest cylinder
⬍0.5D
20 (95) 20 (95) 20 (95) 19 (90) 19 (90) 20 (95)
ⱖ0.5D
1 (5)
1 (5)
1 (5)
2 (10) 2 (10) 1 (5)
D ⫽ diopters; FL ⫽ femtosecond laser; MM ⫽ mechanical microkeratome.
crokeratomes.7,8 Inflammatory cell infiltration increases
with higher side-cut energies (Invest Ophthalmol Vis Sci
2006;47:2733) because of epithelial disruption and release
of proinflammatory cytokines.8,22 Although inflammatory
cell infiltration was not observed by confocal microscopy in
our study, eyes were not examined until 1 month after
surgery, and an early transient inflammatory cell response
may not have been detected. Higher energy levels are also
associated with increased keratocyte death (Invest Ophthalmol Vis Sci 2006;47:2733; Invest Ophthalmol Vis Sci 2006;
47:2731), which triggers a greater wound healing response,
sometimes resulting in haze.23 In our study, keratocyte
activation was qualitatively more apparent after bladeless
LASIK compared with LASIK with the mechanical microkeratome in some subjects, and appeared to diminish in
parallel with haze. Further study is needed to correlate
keratocyte activation after bladeless LASIK to corneal
backscatter. Increased backscatter could have been the result of traumatic flap lifts, which occur for most surgeons
early in their experience with the femtosecond laser. However, all surgeons in the present study had adequate experience with bladeless flap lifts before enrolling patients.
Although corneal backscatter after bladeless LASIK was
higher than after LASIK with the mechanical microkeratome, the differences were small and not visually significant. Corneal haze consists of reflected and backscattered
light,18 neither of which directly affect the image formed on
the retina. Forward light scatter does degrade the retinal
image, and although a relationship between corneal back-
Figure 3. Mesopic contrast sensitivity before and after LASIK (black line ⫽ bladeless; gray line ⫽ mechanical microkeratome). No differences were found
between treatments preoperatively or postoperatively for any spatial frequency. Mesopic contrast sensitivity at 18 cycles/degree increased at 3 months after
LASIK (bladeless, P ⫽ 0.02; mechanical microkeratome, P⬍0.001), but not at 6 months. The dotted line in the postoperative graphs represents
preoperative mesopic contrast sensitivity for comparison.
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Ophthalmology Volume 114, Number 8, August 2007
Table 5. Intraocular Forward Light Scatter
Forward Light Scatter (Stray Light Parameter)
Stray Light Angle
3.5 degrees
Femtosecond laser
Mechanical microkeratome
P (MDD)
10 degrees
Femtosecond laser
Mechanical microkeratome
P (MDD)
28 degrees
Femtosecond laser
Mechanical microkeratome
P (MDD)
Preoperative
1 Month
3 Months
6 Months
0.99⫾0.40*
0.94⫾0.36
⬎0.99 (0.20)
1.03⫾0.33*
1.03⫾0.28
⬎0.99 (0.21)
1.16⫾0.27*
1.14⫾0.19
⬎0.99 (0.14)
1.15⫾0.22
1.08⫾0.21*
0.41 (0.16)
1.09⫾0.36
1.12⫾0.22
⬎0.99 (0.18)
1.13⫾0.20
1.10⫾0.19
⬎0.99 (0.14)
1.22⫾0.20
1.22⫾0.23
⬎0.99 (0.10)
1.23⫾0.22
1.22⫾0.16†
⬎0.99 (0.15)
1.02⫾0.36
1.05⫾0.31
⬎0.99 (0.18)
1.05⫾0.28
1.05⫾0.24
⬎0.99 (0.19)
1.17⫾0.29
1.19⫾0.23
⬎0.99 (0.21)
1.21⫾0.23
1.19⫾0.16
⬎0.99 (0.16)
MDD ⫽ minimum detectable difference (paired data, ␣ ⫽ 0.05/4, ß ⫽ 0.20, n ⫽ 21).
Data are presented as mean values ⫾ standard deviation; n ⫽ 21 unless stated. P values comparing treatments were
adjusted for 4 comparisons by the Bonferroni technique.
*n ⫽ 20 because outlying data (⬇3 standard deviations from the mean) were excluded.
†
P ⫽ 0.04 versus preoperative (after adjusting for 3 comparisons by the Bonferroni technique).
scatter and forward scatter is often inferred, the relationship
is complex.24,25 Nevertheless, increased corneal backscatter
after photorefractive keratectomy has been correlated with
whole eye forward light scatter26 and low-contrast visual
acuity.27 In our study, we were unable to establish a correlation between corneal backscatter and whole eye forward
light scatter or contrast sensitivity, and we postulate that this
was because the increase in backscatter after LASIK is
small compared with that after photorefractive keratectomy.
Forward light scatter within the whole eye did not differ
between methods of flap creation in our study, but because
of the wide variance in forward scatter and the small sample, our study may have lacked sufficient power to detect a
difference (Table 5). Even if a small but clinically significant difference in forward light scatter were to exist between the different methods of flap creation, resulting from
the energy imparted to the corneal stroma during bladeless
flap creation, the difference would be expected to diminish
as the total energy delivered is decreased with 30- and
60-kHz upgrades to the IntraLase femtosecond laser. Although the increase in forward light scatter at 6 months after
LASIK with the mechanical microkeratome was isolated to
stray light incident at 10 degrees and could have arisen by
chance, we are continuing our study to relate long-term
changes in forward scatter with changes in keratocyte density.28
Uncorrected and best-spectacle corrected high-contrast
visual acuity did not differ between treatments at any examination through 6 months in our study. Lim et al.10 and
Kezirian and Stonecipher11 found similar results at 3
months after surgery, whereas Durrie and Kezirian12 found
better UCVA with the femtosecond laser in a paired-eye
randomized study. In the latter study, the difference in
visual acuity between treatments disappeared after controlling for differences in manifest postoperative astigmatism.
Despite our small sample, the minimum detectable statistical differences for uncorrected and best-corrected visual
1488
acuities were approximately 0.1 logMAR or less (Table 2)
at all postoperative examinations. Our study therefore had
sufficient power to detect clinically significant differences
in visual acuity between the 2 treatments. Contrary to
Kezirian and Stonecipher,11 we were unable to detect statistical or clinical differences in residual refractive error or
variance of astigmatism.
Changes in contrast sensitivity after LASIK are variable.
Decreased contrast sensitivity has been reported at low
through high spatial frequencies during the first 3 to 6
months after LASIK, with recovery to preoperative levels
thereafter.29 –32 Mutyala et al33 found little change in contrast sensitivity after LASIK, and Lim et al10 found increased mesopic contrast sensitivity at higher spatial frequencies 3 months after bladeless LASIK but not after
LASIK with a mechanical microkeratome. Although optical
magnification, which occurs after myopic LASIK, may account for some of the increase in contrast sensitivity at
higher spatial frequencies compared with spectacle correction,34 Tuan and Liang35 controlled for optical magnification in a large retrospective analysis, and still found increased contrast sensitivity at all spatial frequencies after
wavefront-guided LASIK. None of the eyes in our study
received wavefront-guided ablations, and yet we found a
small increase in mesopic contrast sensitivity at the highest
spatial frequency at 3 months, but not at 6 months, with both
methods of flap creation. Our results show that contrast
sensitivity can be preserved during the first 6 months after
conventional (non–wavefront-guided) LASIK, regardless of
the method of flap creation.
Bladeless flaps were thicker than intended and mechanical microkeratome flaps were thinner than intended in our
study, with the result that the achieved mean flap thicknesses were similar for both treatments. However, for an
intended bladeless flap thickness of 120 ␮m, Binder measured 122⫾12 ␮m,7 and for an intended bladeless flap
thickness of 130 ␮m, Kezirian and Stonecipher measured
Patel et al 䡠 Femtosecond Laser versus Mechanical Microkeratome
114⫾14 ␮m11; neither study reported whether measured
flap thickness differed significantly from intended flap
thickness. Measured bladeless flap thickness can vary as a
function of intended thickness for an individual femtosecond laser,7 but variability between individual lasers and
differences in the method of flap thickness measurement are
more plausible explanations for the different results between
the aforementioned studies. Binder7 derived flap thickness
from intraoperative ultrasonic pachometry measurements and
Kezirian and Stonecipher11 derived flap thickness from preoperative and intraoperative ultrasonic pachometry measurements, whereas we used confocal microscopy in vivo. Confocal microscopy enables direct visualization of corneal
structures, including the surface epithelium and interface,19,21
enabling accurate thickness measurements.36 Although epithelial hyperplasia has been reported after LASIK and may
affect measurements of flap thickness a month after surgery,21,37–39 we did not detect a significant change in epithelial thickness at 1 month compared with preoperative in
the present study (data not reported).
With a larger sample size, we may have been able to
show a statistical difference in variance of flap thickness
between bladeless and mechanical microkeratome techniques, and therefore greater predictability of flap thickness
with our femtosecond laser.7 The standard deviation of
bladeless flap thickness was within 1 ␮m for individual
surgeons in the study, indicating little variability between
surgeons. However, similar to mechanical microkeratomes,
the femtosecond laser can create much thicker than intended
flaps, by as much as 52 ␮m in our study. Because of the
variation between individual femtosecond lasers, keratorefractive surgeons may need to be cautious about assuming
an intended flap thickness when calculating residual stromal
bed thickness. Furthermore, optical pachometry methods, as
used in our study, indicate lower thickness than ultrasonic
measurements,36 from which residual stromal bed thickness
is routinely calculated. Of note, flap thickness with the
mechanical microkeratome in the present study appears
lower than we reported in a previous study with the same
instrument21 because we recalibrated our confocal microscope after discovering an error in the manufacturer’s calibration.36,39 After recalculating the measurements from our
previous study with the new calibration, flap thickness at 1
month was 143⫾25 ␮m,39 similar to the present study.
One patient was excluded from our study because of an
intraoperative complication. An off-axis “button-hole” flap
was created in the eye treated by the mechanical microkeratome, and was thought to result from a dry spot having
developed while the eye was anesthetized and open during
the femtosecond procedure on the fellow eye. The flap was
immediately replaced and excimer ablation was not performed on either eye at that time. Four months later, the
patient received photorefractive keratectomy to the eye with
the button-hole, and did well postoperatively with uncorrected Snellen visual acuity of 20/15 with ⬎ 1 year of
follow-up. After completion of bladeless LASIK in the
fellow eye by separating and lifting the flap created 4
months previously, uncorrected Snellen visual acuity was
20/20 1 year after surgery.6 Because our study was designed
to examine the long-term changes in keratocyte density and
effects on corneal haze and vision after LASIK, we excluded this patient from our study. Given the good outcome
in both eyes for this patient, we doubt that an intent-to-treat
analysis would have altered the conclusions of our study
with respect to visual outcomes. Although 1 significant flap
creation complication occurred with the mechanical microkeratome, our study was not designed to assess the safety of
the methods of flap creation. The incidence of button-hole
flaps with the Hansatome microkeratome has been estimated to be ⬍0.3%,40 and thus, determining differences in
safety between the femtosecond laser and the mechanical
microkeratome would require a very large prospective study
or a metaanalysis.
The lack of clinically significant differences in vision in
our study during the first 6 months after LASIK suggests
that either method of flap creation is acceptable. Predictability of flap thickness may be better with the femtosecond
laser than with mechanical microkeratomes, but large deviations from intended thickness are possible with both methods. Differences in safety and corneal biomechanics may
exist, but have yet to be demonstrated.
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