Download Visual Quality After Femtosecond Laser Small Incision Lenticule

REVIEW ARTICLe
Visual Quality After
Femtosecond Laser Small Incision Lenticule Extraction
Huamao Miao, MD, PhD, Tian Han, MD, Mi Tian, MD,
Xiaoying Wang, MD, PhD, and Xingtao Zhou, MD, PhD
Abstract: Femtosecond laser small incision lenticule extraction
(SMILE) is a newly developed form of “flapless” corneal refractive surgery with all-in-one technology. Femtosecond laser SMILE is increasingly attractive for both doctors and patients because it is minimally invasive and does not require a flap to be lifted during surgery. It exhibits
many advantages in terms of morphology, biomechanical effects, corneal
wound healing, and nerve rehabilitation. However, visual quality assessment after refractive surgeries is just as important as these advantages and
correlates with patient satisfaction. Evaluation indexes for visual quality
include visual acuity, contrast sensitivity, aberration, intraocular scattering, and so on. This paper reviewed visual quality and patient satisfaction
after SMILE for myopia correction.
Key Words: femtosecond laser, small incision, lenticule extraction,
myopia, visual quality, aberration, scattering, contrast sensitivity
(Asia-Pac J Ophthalmol 2017;0:0–0)
C
orneal refractive surgeries for myopia correction have consistently and rapidly improved; these surgeries have shifted
from using excimer lasers to using femtosecond lasers, from laser
ablation to lenticule extraction, and from large corneal incisions
to small 2-mm incision lenticule extraction. Femtosecond laser
small incision lenticule extraction (SMILE) is a newly developed
form of “flapless” corneal refractive surgery employing all-in-one
technology. To correct myopia and astigmatism, 2 steps are performed in SMILE. First, a convex-shaped lenticule and a 2-mm
upper corneal incision are produced using the femtosecond laser; after this, the lenticule is dissected and extracted through
the 2-mm incision.1 Compared with laser in situ keratomileusis
(LASIK), the small incision necessary for SMILE eliminates
postoperative cap-related complications; moreover, instead of the
2 laser platforms needed in LASIK, SMILE can be completed using only 1 platform, which is more efficient. When compared with
From the Key Laboratory of Myopia, Ministry of Health, Department of
Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai,
China.
Received for publication September 17, 2016; accepted January 19, 2017.
H. M. and T. H. contributed equally to this study and are considered co-first
authors.
Supported in part by the National Natural Science Foundation of China (Grant
No. 81570879) and the Outstanding Academic Leaders Program of Shanghai
Health System (Grant No. XBR2013098).
The authors have no other conflicts of interest to declare.
Reprints: Xingtao Zhou, MD, PhD, Department of Ophthalmology and Vision
Science, Eye and ENT Hospital of Fudan University, No.19 Baoqing Road,
Xuhui District, Shanghai, China. Email: [email protected].
Copyright © 2017 by Asia Pacific Academy of Ophthalmology
ISSN: 2162-0989
DOI: 10.22608/APO.2016171
laser-assisted subepithelial keratomileusis (LASEK), SMILE preserves the epithelium layer and the Bowman membrane, causes
less postoperative corneal irritation, and reduces the risk of haze
development. All of these advantages make SMILE a popular
corneal refractive technique for myopia correction. Clinical and
experimental studies have revealed that SMILE has less of an effect on the corneal nerve and corneal sensitivity than other corneal
refractive surgeries2‒7; furthermore, it potentially reduces corneal
biomechanical stability to a lesser extent than other techniques.8,9
It is of great importance to assess visual performance after refractive surgery. In this review, the main outcomes of recent studies
about objective optical quality and subjective visual quality after
SMILE are summarized.
Visual and Refractive Outcomes
Since 2011, many prospective clinical studies have demonstrated the safety, efficacy, predictability, and stability of SMILE
for myopia and astigmatism correction1,10‒20; the results are summarized below. The visual and refractive results may have differed slightly among studies due to the different inclusion criteria
employed [eg, different ages, preoperative refraction values, and
corrected distant visual acuity (CDVA)], attempted refraction related to the surgery, and country/area in which the surgeries were
performed. Researchers have reported that in patients with a preoperative CDVA of 20/25 or better, 85% to 100% could achieve
a postoperative CDVA of 20/20 or better at 3 or 6 months after
SMILE. Ten to 30% of those patients gained 1 line of CDVA and
4‒10% gained 2 or more lines, though in 50‒80% of patients, the
CDVA remained unchanged. A few patients exhibited CDVA loss
in the earliest period after SMILE; in general, less than 10% of
the patients lost 1 line, and extremely few (less than 3%) lost 2
or more lines of CDVA. Even so, some of the CDVA loss was recovered in the long run (6 months or more). In Vestergaard et al’s
study,10 they observed that decentered optical zone, dryness, interface scattering, and irregular topography were several reasons
for the loss of CDVA. Donate et al21 found that an energy level
close to the plasma threshold [a cut energy index of 20 (100 nJ)]
during SMILE provides a faster and better visual recovery.21 Ultimately, more than 90% of the patients had a postoperative uncorrected distance visual acuity (UDVA) reaching 20/40 or better
and more than 60% reaching 20/20 or better at 3 or 6 months after
SMILE.1,10‒17
By the 3-month or 6-month follow-up in previous clinical
studies,1,10‒18 90% or more eyes were within ±0.5 diopters (D) and
95% were within ±1.00 D of the target refraction. A strong consistency was found between the achieved correction and the attempted refraction, with a correlation coefficient of 0.9 or higher. Visual acuity and refraction usually began to achieve stability from
1 week or 1 month postoperatively. Hjortdal et al11 found that
Asia-Pacific Journal of Ophthalmology • Volume 0, Number 0, Month 2017
Copyright © 2017 Asia-Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
www.apjo.org |
Miao et al
Asia-Pacific Journal of Ophthalmology • Volume 0, Number 0, Month 2017
a small undercorrection was associated with older age (0.10 D
per decade) and steeper corneal curvature (0.04 D per D). However, this finding could partly be affected by the operative design
where a small residual myopic correction was performed in patients older than 40 years.
Some recent studies reported longer-term results after
SMILE. Miao et al22 found consistent UDVA and CDVA values
at 6 and 18 months after SMILE for moderate to high myopia
correction. At 18 months postoperatively, 67% of the eyes gained
1 or more lines of CDVA, and none lost 2 or more lines. In addition, 91% and 100% of the eyes were within ±0.5 D and ±1.0 D
of the intended refraction at 18 months, respectively. The mean
spherical equivalent (SE) was −0.19 D at 6 months and regressed
slightly to −0.23 D at 18 months, but the cylindrical diopters remained unchanged. Han et al19 found no significant regression between 4-year and 6-month outcomes. Pederson et al23 compared
the outcomes 3 months and 3 years after SMILE and found no
difference in UDVA, though CDVA increased by −0.03 logMAR;
in this study 78% and 90% of the eyes were within ±0.5 D and
±1.0 D of the target refraction at 3 years, respectively. No difference in SE was observed between the 2 follow-up times (−0.31 D
to −0.39 D). Although a minor regression (0.36 D) of total corneal refractive power was detected, no significant change in SE
was observed. A 5-year observation of the first group of patients
treated with SMILE worldwide was reported by Blum et al24; by
5 years, 58% of the 56 eyes gained 1 to 2 lines of CDVA, and
48.2% and 78.6% of the eyes were within ±0.5 D and ±1.0 D of
the intended refraction, respectively. A mean regression of 0.48 D
was observed, although this was mainly due to 7 eyes; 6 of these
eyes exhibited an axial length (AL) elongation rather than a steepening of the cornea, and the other eye showed cap perforation
resulting in corneal scarring. Overall, refractive regression tends
to increase with time, and it seems to be mostly caused by AL
elongation; however, the SMILE regression data are no worse
than the data from other keratorefractive procedures.
Contrast Sensitivity
Visual acuity is an overall parameter to measure the eye’s
ability to recognize objects of different sizes at the 100% contrast level. However, contrast sensitivity testing provides a more
comprehensive description of visual function than the standard
visual acuity chart testing; it is a measure of the ability to discern
objects of different sizes and contrasts. Contrast sensitivity was
also investigated after SMILE. Sekundo et al12 used the Vector
Vision CSV 1000E Test to measure contrast sensitivity at 3, 6, 12,
and 18 cycles per degree (cpd) 1 year after SMILE. No significant postoperative contrast sensitivity change was found in either
the photopic or scotopic environment, and the contrast sensitivity
at different partial frequencies showed stability at different time
points. Similarly, in Vestergaard et al’s study,13 no significant contrast sensitivity change was found 6 months after SMILE. These
results suggested that SMILE had little influence on the formsense function of the visual system; they also showed that postoperative contrast sensitivity was stable.
Higher-Order Aberrations
Higher-order aberrations (HOAs) can increase after corneal
refractive surgeries. Consistent results concerning HOA changes
| www.apjo.org
after SMILE have been reported. Shah et al14 reported that total HOAs, coma, spherical aberration, and residual fourth-order
astigmatism increased significantly at 6 months postoperatively.
Moreover, Sekundo et al12 found that HOAs increased from 0.17 ±
0.08 μm to 0.27 ± 0.10 μm, coma from 0.28 ± 0.19 μm to 0.55 ±
0.30 μm, and spherical aberration from −0.01 ± 0.23 μm to −0.12 ±
0.20 μm at 1 year postoperatively. Different components of HOAs
changed differently. Previously, Miao et al22 analyzed aberration
changes 18 months after SMILE; we found that the total HOAs,
spherical aberration, and coma increased significantly, but no significant change in trefoil or tetrafoil was observed. Among these
aberrations, coma was induced most, and the changes in HOAs
were consistent with the changes in coma; thus, we suggested
that the postoperative total HOA induction was mainly due to the
coma increase.
Postoperative induced coma may be associated with a mild
decentration. Li et al15 revealed that vertical coma showed the
greatest increase in magnitude; this was found to be associated
with the magnitude of horizontal decentration. Moreover, according to Wu et al’s study,25 SE together with corneal resistance factor (CRF) showed a negative liner relationship with changes of
third- to sixth-order HOAs and spherical aberration but a positive
linear relationship with changes of vertical coma.
Long-term changes of spherical aberrations were also observed. Spherical aberrations increased at 6 months after SMILE
in our previous study; however, the difference no longer existed
at 18 months.22 Pedersen et al23 found that corneal spherical aberration and total corneal HOAs decreased from 3 months to 3 years
while coma remained stable. Han et al19 found that no significant
changes in whole-eye aberrations were detected among the 1month, 6-month, or 4-year follow-ups postoperatively.
When compared with other corneal refractive surgeries,
SMILE induces fewer postoperative HOAs. For example, total
HOAs and spherical aberration were induced less after SMILE than
after LASEK, whereas coma was induced at a similar rate.26 When
compared with femtosecond laser‒assisted LASIK (FS-LASIK),
more coma was induced after SMILE. Yao et al16 observed aberrations more than 3 months after SMILE and FS-LASIK; they
found that HOAs and coma increased in both groups, and spherical aberration increased in the FS-LASIK group. The increase of
coma was greater in the SMILE group, whereas the increase in
spherical aberration was greater in the FS-LASIK group. Lin et
al17 also found that total HOAs, spherical aberration, and coma
increased after both surgeries, whereas total HOAs and spherical
aberration were induced less after SMILE, and coma was induced
less after FS-LASIK at 3 months. Two studies compared SMILE
and femtosecond lenticule extraction (FLEx) groups and found
similar aberration changes.13,20
Intraocular Scattering
Due to the microcosmic nonhomogeneity characteristics and
different refractive indexes of ocular refractive media, light scatters as it follows its pathway and forms intraocular scatter light.
An excessive amount of intraocular scattering projecting to the
retina could reduce the contrast sensitivity and cause unsatisfactory visual performance. Intraocular scatter light could increase
after refractive surgery.27,28 When evaluating the retinal image
quality after SMILE, it is essential to take intraocular scattering
changes into consideration. Our study used a double-pass system
© 2017 Asia-Pacific Academy of Ophthalmology
Copyright © 2017 Asia-Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
Asia-Pacific Journal of Ophthalmology • Volume 0, Number 0, Month 2017
to evaluate objective forward scatter light after SMILE and found
that postoperative intraocular scattering had a tendency to increase temporarily and then decrease to preoperative baseline in
3 months; however, the increase was within an acceptable range.
Moreover, lower postoperative intraocular scattering was associated with younger age, lower preoperative refractive degree, and
lower preoperative intraocular scattering.29 Our further study suggested that stable postoperative intraocular scattering may occur
for a longer period; we found that intraocular scattering levels at 6
and 18 months after SMILE were not significantly different from
the preoperative level.22 Agca et al30 used in vivo confocal microscopy to evaluate corneal backscattering after SMILE; they found
that the backscattered light increased after SMILE in the early
period and then decreased to the preoperative level at 6 months.
Xu et al31 used a subjective method (C-quant) to measure the postoperative scatter light and found a 58% increase at 1 month after
SMILE and a 51% increase at 1 year. However, the increases did
not exhibit statistical significance. In addition, they found that
SMILE induced less postoperative scatter light when compared
with LASIK and epipolis LASIK (Epi-LASIK). Haze and anterior keratocyte loss were considered to relate to the scatter light
increase after excimer laser surgeries, and this could be associated with corneal wound healing.32‒35 However, further study is
needed to investigate the mechanism of a temporary intraocular
scattering increase after SMILE.
Patient Satisfaction
Patient satisfaction comprises the patient’s overall feeling
about the surgery and is part of a comprehensive assessment of
visual quality. Sekundo et al1 carried out a questionnaire survey
administered to 48 patients 6 months after SMILE; the mean
quality of vision was graded at 92.3 on a scale of 0 (very poor) to
100 (best ever known). All eyes exhibited improved vision; it was
found that 28.4% were markedly improved, 68.2% were extremely improved, and 3.4% were somewhat improved. Furthermore,
93.3% of the patients indicated that they would undergo the procedure again. The remaining 6.7% were not sure if they would do
so again because they had some trouble with night vision or driving at night. None of the respondents complained of glare, whereas 7.7% reported dryness compared with 2.2% before the surgery.
Shah et al14 conducted a survey at 3 months postoperatively in 41
patients; the most common complaint was mild dryness, but no
patients complained about the increase of halos, double vision, or
night-driving vision deterioration. In addition, on a scale from 0
(very dissatisfied) to 10 (very satisfied), all patients reported being very satisfied with the treatment. The mean satisfaction was
9.3 ± 1.1 on a scale of 0‒10 at 3 months postoperatively in Vestergaard et al’s study.10 Here, 95% of patients were willing to recommend the treatment to others. Marked to extreme improvement
of overall quality of vision was reported in 95% of the patients,
4% perceived that it was moderately improved, and 1% perceived
that it was not or only slightly improved. A comparative study
included 34 patients who received SMILE in 1 eye and FLEx in
the other; the mean satisfaction score was 9.3 ± 1.1 on a scale of
0‒10, with no difference between the 2 treatments.13
Investigations using larger sample sizes and longer-term follow-up studies also showed high patient satisfaction after SMILE.
Ivarsen et al18 reported that the mean 3-month satisfaction score
in 1036 eyes of 808 patients was 9.34, whereas 6 patients (9 eyes)
Visual Quality After SMILE
reported a score of 5 or less. The unsatisfied patients complained
about monocular ghost images, blurred vision due to haze, unstable vision due to dryness, or residual cylinder due to preoperative high cylindrical diopters beyond the treatment range. After
treatment, some of the symptoms were ameliorated, and only 2
patients were still dissatisfied at the last visit (more than 1 year
later) due to blurred vision or residual astigmatism. Our study
reported that the mean 18-month satisfaction score for SMILE
was 9.31 ± 0.64; this study found that 47.83% of the patients were
very satisfied and 52.17% were satisfied, whereas no patient was
unsatisfied.22
Conclusions
In conclusion, SMILE is a safe, effective, and highly satisfactory procedure for myopia correction. The visual and refractive
outcomes exhibit stability soon after the treatment, and contract
sensitivity at different spatial frequencies is barely influenced.
However, younger patients should be reminded of possible refractive regression due to their continued AL elongation. Finally,
we suggest that future studies on the following topics may help to
elucidate visual quality after SMILE: (1) coma was induced most
after SMILE; therefore, optimization of the surgical technique to
reduce coma is needed in the future; (2) long-term corneal remodeling might lead to the decrease of certain components of HOAs
after SMILE and this regularity could be further observed; and
(3) a temporary increase of intraocular scattering after SMILE
was detected; the reason for this needs to be further discussed,
and this may be helpful in improving optical quality in the early
period and patient satisfaction.
References
1. Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery
using the small incision lenticule extraction (SMILE) procedure for the
correction of myopia and myopic astigmatism: results of a 6 month
prospective study. Br J Ophthalmol. 2011;95:335‒339.
2. Dong Z, Zhou X, Wu J, et al. Small incision lenticule extraction (SMILE)
and femtosecond laser LASIK: comparison of corneal wound healing and
inflammation. Br J Ophthalmol. 2014;98:263‒269.
3. Vestergaard AH, Gronbech KT, Grauslund J, et al. Subbasal nerve
morphology, corneal sensation, and tear film evaluation after refractive
femtosecond laser lenticule extraction. Graefes Arch Clin Exp Ophthalmol.
2013;251:2591‒2600.
4. Li M, Niu L, Qin B, et al. Confocal comparison of corneal reinnervation
after small incision lenticule extraction (SMILE) and femtosecond laser in
situ keratomileusis (FS-LASIK). PLoS One. 2013;8:e81435.
5. Denoyer A, Landman E, Trinh L, et al. Dry eye disease after refractive
surgery: comparative outcomes of small incision lenticule extraction versus
LASIK. Ophthalmology. 2015;122:669‒676.
6. Wei S, Wang Y. Comparison of corneal sensitivity between FS-LASIK
and femtosecond lenticule extraction (ReLEx flex) or small-incision
lenticule extraction (ReLEx smile) for myopic eyes. Graefes Arch Clin Exp
Ophthalmol. 2013;251:1645‒1654.
7. Li M, Zhou Z, Shen Y, et al. Comparison of corneal sensation between
small incision lenticule extraction (SMILE) and femtosecond laser-assisted
LASIK for myopia. J Refract Surg. 2014;30:94‒100.
8. Wu D, Wang Y, Zhang L, et al. Corneal biomechanical effects: smallincision lenticule extraction versus femtosecond laser-assisted laser in situ
keratomileusis. J Cataract Refract Surg. 2014;40:954‒962.
© 2017 Asia-Pacific Academy of Ophthalmology
Copyright © 2017 Asia-Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
www.apjo.org |
Miao et al
Asia-Pacific Journal of Ophthalmology • Volume 0, Number 0, Month 2017
9. Vestergaard AH, Grauslund J, Ivarsen AR, et al. Central corneal sublayer
pachymetry and biomechanical properties after refractive femtosecond
lenticule extraction. J Refract Surg. 2014;30:102‒108.
10. Vestergaard A, Ivarsen AR, Asp S, et al. Small-incision lenticule extraction
for moderate to high myopia: predictability, safety, and patient satisfaction.
J Cataract Refract Surg. 2012;38:2003‒2010.
11. Hjortdal JO, Vestergaard AH, Ivarsen A, et al. Predictors for the outcome
prospective study. J Refract Surg. 2015;31:726‒731.
23. Pedersen IB, Ivarsen A, Hjortdal J. Three-year results of small incision
lenticule extraction for high myopia: refractive outcomes and aberrations. J
Refract Surg. 2015;31:719‒724.
24. Blum M, Taubig K, Gruhn C, et al. Five-year results of small incision
lenticule extraction (ReLEx SMILE). Br J Ophthalmol. 2016;100:1192‒1195.
25. Wu W, Wang Y. The correlation analysis between corneal biomechanical
of small-incision lenticule extraction for myopia. J Refract Surg. 2012;28:
properties and the surgically induced corneal high-order aberrations after
865‒871.
small incision lenticule extraction and femtosecond laser in situ
12. Sekundo W, Gertnere J, Bertelmann T, et al. One-year refractive results,
contrast sensitivity, high-order aberrations and complications after myopic
small-incision lenticule extraction (ReLEx SMILE). Graefes Arch Clin Exp
Ophthalmol. 2014;252:837‒843.
13. Vestergaard AH, Grauslund J, Ivarsen AR, et al. Efficacy, safety,
predictability, contrast sensitivity, and aberrations after femtosecond laser
lenticule extraction. J Cataract Refract Surg. 2014;40:403‒411.
14. Shah R, Shah S, Sengupta S. Results of small incision lenticule extraction:
all-in-one femtosecond laser refractive surgery. J Cataract Refract Surg.
2011;37:127‒137.
keratomileusis. J Ophthalmol. 2015;2015:758196.
26. Yu M, Chen M, Wang B, et al. Comparison of visual quality after SMILE and
LASEK for mild to moderate myopia. J Refract Surg. 2015;31:795‒800.
27. van Bree MC, van Verre HP, Devreese MT, et al. Straylight values after
refractive surgery: screening for ocular fitness in demanding professions.
Ophthalmology. 2011;118:945‒953.
28. Braunstein RE, Jain S, McCally RL, et al. Objective measurement of
corneal light scattering after excimer laser keratectomy. Ophthalmology.
1996;103:439‒443.
29. Miao H, He L, Shen Y, et al. Optical quality and intraocular scattering
15. Li M, Zhao J, Miao H, et al. Mild decentration measured by a Scheimpflug
camera and its impact on visual quality following SMILE in the early
learning curve. Invest Ophthalmol Vis Sci. 2014;55:3886‒3892.
16. Yao P, Zhao J, Li M, et al. Microdistortions in Bowman’s layer following
femtosecond laser small incision lenticule extraction observed by Fourierdomain OCT. J Refract Surg. 2013;29:668‒674.
17. Lin F, Xu Y, Yang Y. Comparison of the visual results after SMILE and
femtosecond laser-assisted LASIK for myopia. J Refract Surg. 2014;30:
after femtosecond laser small incision lenticule extraction. J Refract Surg.
2014;30:296‒302.
30. Agca A, Ozgurhan EB, Yildirim Y, et al. Corneal backscatter analysis by
in vivo confocal microscopy: fellow eye comparison of small incision
lenticule extraction and femtosecond laser-assisted LASIK. J Ophthalmol.
2014;2014:265012.
31. Xu L, Wang Y, Li J, et al. Comparison of forward light scatter changes
between SMILE, femtosecond laser-assisted LASIK, and epipolis LASIK:
results of a 1-year prospective study. J Refract Surg. 2015;31:752‒758.
248‒254.
18. Ivarsen A, Asp S, Hjortdal J. Safety and complications of more than 1500
small-incision lenticule extraction procedures. Ophthalmology. 2014;121:
32. Mohan RR, Hutcheon AE, Choi R, et al. Apoptosis, necrosis, proliferation,
and myofibroblast generation in the stroma following LASIK and PRK. Exp
Eye Res. 2003;76:71‒87.
822‒828.
19. Han T, Zheng K, Chen Y, et al. Four-year observation of predictability and
stability of small incision lenticule extraction. BMC Ophthalmol. 2016;16:149.
20. Agca A, Demirok A, Cankaya KI, et al. Comparison of visual acuity and
higher-order aberrations after femtosecond lenticule extraction and smallincision lenticule extraction. Cont Lens Anterior Eye. 2014;37:292‒296.
21. Donate D, Thaeron R. Lower energy levels improve visual recovery in small
incision lenticule extraction (SMILE). J Refract Surg. 2016;32:636‒642.
33. Nieto-Bona A, Lorente-Velazquez A, Collar CV, et al. Intraocular
straylight and corneal morphology six months after LASIK. Curr Eye Res.
2010;35:212‒219.
34. Ivarsen A, Laurberg T, Moller-Pedersen T. Role of keratocyte loss on
corneal wound repair after LASIK. Invest Ophthalmol Vis Sci. 2004;45:
3499‒3506.
35. Vignal R, Tanzer D, Brunstetter T, et al. [Scattered light and glare sensitivity
22. Miao H, Tian M, Xu Y, et al. Visual outcomes and optical quality after
after wavefront-guided photorefractive keratectomy (WFG-PRK) and laser
femtosecond laser small incision lenticule extraction: an 18-month
in situ keratomileusis (WFG-LASIK)]. J Fr Ophtalmol. 2008;31:489‒493.
| www.apjo.org
© 2017 Asia-Pacific Academy of Ophthalmology
Copyright © 2017 Asia-Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.