Department of Human Genetics and Public Health, Graduate
School of Proteomics, The University of Tokushima, Tokushima,
Japan
Abstract: Objective: To evaluate the effectiveness of laser
in situ keratomileusis (LASIK) and photorefractive keratectomy
(PRK) for correcting myopia.
Methods: Study selection, data extraction, and quality assessment
were performed by two of authors independently. Summary
odds ratios and 95% confidence intervals were calculated
by DerSimonian & Laird random-effects model and Mantel-Haenszel
(fixed-effects) model. All calculations were based on an
intention-to-treat and per protocol analysis.
Results: Five hundred and eighty eyes (476 patients) from
5 randomized controlled trials were included in this study.
At>=6 months follow-up, by random-effects model, the
pooled odds ratios (OR, for LASIK vs. PRK) of postoperative
uncorrected visual acuity (UCVA) of20/20 or better for all
trials were 1.31 (95% CI=0.77-2.22) by per protocol analysis
and 1.18 (95%CI=0.74-1.88) by intention-to-treat analysis.
In the refractive outcome, the pooled OR of the postoperative
spherical equivalent refraction within±0.5 diopter
(D) of emmetropia did not show any statistical significance,
for which the OR were 0.75 (95% CI=0.48-1.18) by per protocol
analysis and0.70 (95%CI=0.47-1.04) by intention-to-treat
analysis.
Conclusions: LASIK and PRK were found to be similarly effective
for the correction of myopia from-1.5to -15.0D in a greater
than6month follow-up. J. Med. Invest. 50 : 180-186, 2003
Keywords:laser in situ keratomileusis (LASIK), photorefractive
keratectomy (PRK), myopia, meta-analysis
INTRODUCTION
Since Trokel and coauthors introduced photorefractive keratectomy
(PRK) in1983 (1), numerous studies have been done on this
procedure. The refractive surgery using a 193 nm argon fluoride
excimer laser has become a reasonably predictable, effective,
and safe method for treating low to moderate myopia (2-7).
Its major limitations are postoperative pain, subepithelial
haze, and prolonged visual rehabilitation (8, 9). Laser
in situ keratomileusis (LASIK) combines lamellar corneal
surgery with the accuracy of the excimer laser. It is a
procedure that has evolved from a variety of techniques
in refractive surgery. The first LASIK procedure on the
human eye was performed by Pallikaris and coauthors in 1991
(10, 11). Since then, this procedure has gradually become
more popular, particularly among high-volume refractive
surgeons. LASIK offers more comfort, faster visual rehabilitation,
and minimal haze, but epithelial ingrowths, corneal-flap-related
complications, and corneal ectasia are shortcomings of LASIK
(12-15). To date, a number of studies have reported the
results that both techniques effectively correct varying
degrees of myopia. Although several prospective or retrospective
controlled trials have been suggested for the advantages
of LASIK over PRK (16 -20), several well-designed randomized
controlled clinical trials indicated that the efficacy outcomes
in the longer term are generally similar between the two
procedures for correcting low to high myopia (21-24). In
this study, we have summarized the published randomized
controlled trials of PRK and LASIK, for correcting myopia,
to quantitatively evaluate the effectiveness of myopia treatment
with both PRK and LASIK procedures.
METHODS
Data sources
Studies were identified by MEDLINE and EMBASE searches through
October 2002. The terms photorefractive keratectomy and
laser in situ keratomileusis, and myopia or refractive myopia,
were used for a sensitive search. In addition, we limited
publication types to Randomized Controlled Trial. Bibliographies
of retrieved articles were manually searched.
Study selection
We included English-language studies that met all of the
following criteria, as judged independently by two investigators
(Yang and Yan) : (1) a prospective, randomized controlled
clinical trial, (2) comparison study for effectiveness,
safety, and stability of PRK and LASIK for correcting myopia,(3)
main outcome measures included manifest refraction, uncorrected
and spectacle-corrected visual acuity, predictability and
stability of refraction, and complications, (4) original
data of every follow-up time was available. Reviews, abstracts
and articles published in non-English languages were excluded.
Assessment of study quality
The quality of the included studies was assessed using the
criteria proposed by Chalmers et al.(25).This method evaluates
the design, implementation, and analysis, of randomized
controlled trials. The overall index of trial quality was
weighted as follows:trial design and protocol, 0.6 ; statistical
analysis, 0.3 ; presentation of results, 0.1. The final
quality score ranged from0 (lowest) to1(highest).
Data extraction
Data extraction was done independently by two authors (Yang
and Yan) using a predefined review form. Postoperative outcome
of refraction, visual outcome, and loss of spectacle-corrected
visual acuity, were calculated by intention-to treat and
per protocol analyses. Any discrepancies between the authors
in data extraction were resolved through discussion to reach
a consensus of opinion.
Statistical analysis
We pooled all the data using the DerSimonian and Laird random-
effects model that considers both within-study variance
and variability among studies. The Mantel-Haenszel (fixed-effects)
model was also used for comparison calculations;this approach
allowed us to verify the validity of the random- effects
estimates in some analyses in which the numbers of events
were small. All estimated odds ratios (OR) were for the
LASIK group compared with the PRK group. Summary estimates
of effect were calculated with weighting based on the inverse
of the study's variance. Two -tailed P values and a 95 percent
confidence interval (95% CI) were used.
The heterogeneity between studies was examined by DerSimonian
and Laird Q statistic (26). Egger's linear regression approach
(27) and Begg and Mazumdar's proposed adjusted rank correlation
test (28) were used to measure publication bias. Sensitivity
analysis was also performed by comparing the overall effect
of different statistical models calculated to assess the
reliability of meta-analysis.
All statistic analyses were carried out using Metaview3.1in
Rev Man 4.04(Cochrane Collaboration, Oxford, England) and
SPSS version 11.0 (SPSS, Inc., Chicago, Illinois).
RESULTS
Study characteristics and quality score
A total of 15 studies were initially identified by two computerized
database and manual searches as potentially relevant. Ten
of these 15 studies were excluded because they did not meet
our criteria (Among those, one was comparison of the effect
of laser epithelial keratomileusis (LASEK) and PRK and other
nine were a paper about the side effects after the operation
of the LASIK and PRK). Five prospective, randomized controlled
trials were included in this meta-analysis (21-24, 29).
The characteristics of the studies are presented in Table
1. A total of 580 eyes (476 patients) were enrolled in the
five trials. Preoperative manifest spherical equivalent
refraction ranged from -1.25 to -14.38 diopter (D). The
follow-up ranged from6months to12months. The studies had
a mean quality score of 0.73 (range, 0.71to0.77), which
was considered to be high compared with the scores of trials
in other clinical domains (30).
Pooling all 5 trials, the characteristics of the patients
receiving PRK or LASIK had no significant differences (Table2).
Pooling of Uncorrected Visual Acuity
Figure 1 shows the odds ratios (OR) for postoperative uncorrected
visual acuity (UCVA) of 20/20 or better at a follow-up>=6
months. Using both random-effects model and fixed-effects
model analyses, the pooled OR were virtually identical,
and there were no statistically significant differences
between LASIK and PRK. The Q statistic did not indicate
significant heterogeneity (Q=5.31, 4 degrees of freedom,
P>0.1). Uncorrected visual acuity of 20/20 or better
after LASIK was 48%and 42% after PRK. Improvement in uncorrected
visual acuity in the LASIK group occurred significantly
faster than in the PRK group. The pooled OR of UCVA>=20/20
are presented in Table 3 ; at 2 weeks, the ORs showed statistical
significances, but after this, the difference was not statistically
significant.
Pooled Refractive Outcome
The results of the postoperative spherical equivalent refraction
within±1.0 D (SE±1.0 D) and±0.5
D (SE±0.5D) of emmetropia were analyzed. At a
follow-up of greater than or equal to 6 months, using the
random-effects-model analysis, the pooled OR of SE±1.0D
were0.64 (95% CI=0.41-1.02) for per protocol analysis and0.63
(95% CI=0.43-0.92) for intention-to-treat analysis ; the
latter shows statistical significance. However, no statistically
significant differences were found in the pooled OR of SE±0.5D
between LASIK and PRK;the OR were 0.75 (95% CI=0.48-1.18)
for per protocol analysis and0.70 (95%CI=0.47-1.04) for
intention-to-treat analysis (Figure2). Using fixed-effects
model analysis, the same results were achieved (data not
shown).
Loss of Spectacle-Corrected Visual Acuity
The following refers to the outcome of loss of spectacle-corrected
visual acuity of two Snellen lines or more at >=6months
follow-up, and the statistically significant differences
between LASIK and PRK. For the per protocol analysis, the
pooled OR were0.32 (95%CI=0.11-0.96, D&L method) and
0.30 (95% CI=0.11-0.85,M-H method) ; for the intention-to-treat
analysis, the OR were 0.31 (95% CI=0.10-0.89, D&L method)
and 0.28(95% CI=0.10-0.79, M-H method). Therefore, the results
suggest a lesser likelihood of loss of spectacle - corrected
visual acuity with LASIK compared with that of PRK.
Subgroup analysis
For low to moderate myopia (-1.5 to - 8.0 D) (Ref 23,24,
29), the pooled OR for UCVA>=20/20and the refractive
outcome (SE±1.0 D and SE±0.5 D) showed
no statistically significant differences between the two
procedures. For moderate to high myopia (-6.0 to -15.0 D)(Ref
21, 22), the pooled OR for refractive outcome showed statistical
significances, namely PRK-treated eyes had a higher percentage
of success than LASIK at>=6months follow-up. There were
no statistically significant differences for the UCVA of
20/20 or better results between LASIK and PRK (Table4).
Complications
The following refers to the subepithelial haze seen in PRK-treated
eyes at 6and12 months follow-up. The subepithlial haze decreased
trace haze (1+) was31.9% (36/113), mild haze (2+) was 6.0%
(10/167), moderate haze (3+) was 4.4% (3/68), and severe
haze (4+)was 3.3% (1/30). After LASIK, the subepithelial
haze was not seen, but there were 4.4% (13/295) flap - related
complications. These events included free cap, stopping
of microkeratome in the middle of the pass, and incomplete,
slipped, or dislocated flaps. No other adverse reactions,
such as microbial keratitis, endophthalmitis, corneal melting
or perforation, corneal ectasia, or retinal lesions, were
found in these studies.
Publication bias and sensitivity analysis
The measure of funnel plot asymmetry showed no statistical
significance with either the regression test or with the
rank correlation test;the P values were0.5 and 0.327, respectively.
Sensitivity analysis was performed using the DerSimonian
& Laird random effects model and the Mantel-Haenszel
method (fixed effects model) to calculate the overall effects.
The results showed that the overall estimates were virtually
identical, and that the confidence intervals were similar
between the random effects model and the fixed - effects
model (data not shown). This was explained by the relatively
small amount of variation between the trials in this meta-analysis.
DISCUSSION
Analyses of the host immune responses are required to study
the molecular pathologic mechanisms of IAV. The infected
epithelial cells and inflammatory leukocytes produce a variety
of chemotactic, proinflammatory, and other immunoregulatory
cytokines. The increase in expression of cytokine genes
is associated with the activation of NF-κB, AP-1,
STAT and IRF signal-transducing molecules in the infected
cells (22-26). We found a significant increase in the expression
of E-selectin, vascular cellular adhesion molecule-1 (V-CAM-1),
macrophage inflammatory protein-2 (MIP-2), inducible nitric
oxide synthase (iNOS) and endothelin-1 (ET-1) mRNAs, along
with an increase in IAV-RNA in the brain of WT mice after
IAV infection, whereas these mRNAs were undetectable in
absence of infection (Fig. 2). Among the mRNAs tested, the
greatest increases in the expressions of ET-1 and iNOS mRNAs
were detected in the brain. These proteins have been reported
to trigger the formation of edema in various tissues. TNF-α
is a pro-inflammatory cytokine that causes apoptotic tissue
injury and a potent inhibitor of mitochondrial respiration.
It prominently induces the mitochondrial permeability transition
(MPT) in living cells, resulting in a necrotic and apoptotic
cell death. Thus, an abrupt increase in TNF-α concentrations
after virus infection in the systemic circulation induces
systemic MPT in multiple organs, and MPT in cerebral capillary
cells cause brain edema in acute IAV encephalopathy or encephalitis
(27). We have found that the concentrations of TNF-α
in the brain of IAV-infected WT newborn mice were significantly
increased on day 5 after inoculation, and that treatment
with diclofenac further increased these concentrations (Fig.
3). Since some cytokines, such as IFN-α/β, IFN-r,
and IL-2, are protective against influenza infection, whereas
others, such as IL-1, TNF-α and IL-6, are involved
in the progression of inflammation (26), further studies
of the concentrations of other cytokines in the brain, and
studies of their mutual interactions are required to elucidate
the pathogenesis of IAV encephalitis.
REFFERENCES
1.Trokel SL, Srinivasan R, Braren B : Excimer laser surgery
of the cornea. Am J Ophthalmol96:710-5, 1983
2.Seiler T, Wollensak J:Myopic photorefractive keratectomy
with the excimer laser. One-year follow-up. Ophthalmology98:1156
- 63, 1991
3.Gartry DS, Kerr Muir MG, Marshall J : Excimer laser photorefractive
keratectomy. 18 - month follow-up. Ophthalmology99:1209-19,
1992
4.Epstein D, Fagerholm P, Hamberg-Nystrom H, Tengroth B:Twenty-four-month
follow-up of excimer laser photorefractive keratectomy for
myopia. Refractive and visual acuity results. Ophthalmology101:1558
- 63;discussion1563-4, 1994
5.Dutt S, Steinert RF, Raizman MB, Puliafito CA : One-year
results of excimer laser photorefractive keratectomy for
low to moderate myopia. Arch Ophthalmol 112:1427-36, 1994
6.Hersh PS, Stulting RD, Steinert RF, Waring GO ?, Thompson
KP, O'Connell M, Doney K, Schein OD:Results of phase ? excimer
laser photorefractive keratectomy for myopia. The Summit
PRK Study Group. Ophthalmology104:1535-53, 1997
7.McDonald MB, Deitz MR, Frantz JM, Kraff MC, Krueger RR,
Salz JJ, Kraff CR, Maguen E, Matta CS, Nesburn AB, Piebenga
LW: Photorefractive keratectomy for low-to -moderate myopia
and astigmatism with a small-beam, tracker- directed excimer
laser. Ophthalmology106:1481-8;discussion1488-9, 1999
8.Steinert RF, Bafna S : Surgical correction of moderate
myopia : which method should you choose? ?. PRK and LASIK
are the treatments of choice. Surv Ophthalmol43:157-79,
1998
9.Bower KS, Weichel ED, Kim TJ:Overview of refractive surgery.
Am Fam Physician 64 : 1183-90, 2001
10.Pallikaris IG, Papatzanaki ME, Siganos DS, Tsilimbaris
MK:A corneal flap technique for laser in situ keratomileusis.
Human studies. Arch Ophthalmol109:1699-702, 1991
11.Pallikaris IG, Papatzanaki ME, Stathi EZ, Frenschock
O, Georgiadis A : Laser in situ keratomileusis. Lasers Surg
Med10:463-8, 1990
12.Farah SG, Azar DT, Gurdal C, Wong J : Laser in situ keratomileusis
: literature review of a developing technique. J Cataract
Refract Surg 24:989-1006, 1998
13.Salah T, Waring GO 3rd, el Maghraby A, Moadel K, Grimm
SB : Excimer laser in situ keratomileusis under a corneal
flap for myopia of 2 to 20 diopters. Am J Ophthalmol121:143-55,
1996
14.Gimbel HV, van Westenbrugge JA, Penno EE, Ferensowicz
M, Feinerman GA, Chen R : Simultaneous bilateral laser in
situ keratomileusis : safety and efficacy. Ophthalmology
106:1461-7;discussion1467-8, 1999
15.Maldonado-Bas A, Onnis R:Results of laser in situ keratomileusis
in different degrees of myopia. Ophthalmology105:606 -11,
1998
16.Pallikaris IG, Siganos DS : Excimer laser in situ keratomileusis
and photorefractive keratectomy for correction of high myopia.
J Refract Corneal Surg10:498-510, 1994
17.Helmy SA, Salah A, Badawy TT, Sidky AN: Photorefractive
keratectomy and laser in situ keratomileusis for myopia
between 6.00 and 10.00diopters. J Refract Surg12:417-21,
1996
18.Wang Z, Chen J, Yang B : Comparison of laser in situ
keratomileusis and photorefractive keratectomy to correct
myopia from -1.25 to - 6.00 diopters.
J Refract Surg13:528 -34, 1997
19.Fernandez AP, Jaramillo J, Jaramillo M:Comparison of
photorefractive keratectomy and laser in situ keratomileusis
for myopia of - 6 D or less using the Nidek EC-5000laser.
J Refract Surg16:711-5, 2000
20.Tole DM, McCarty DJ, Couper T, Taylor HR: Comparison
of laser in situ keratomileusis and photorefractive keratectomy
for the correction of myopia of -6.00diopters or less. Melbourne
Excimer Laser Group. J Refract Surg17:46-54, 2001
21.Hersh PS, Brint SF, Maloney RK, Durrie DS, Gordon M,
Michelson MA, Thompson VM, Berkeley RB, Schein OD, Steinert
RF:Photorefractive keratectomy versus laser in situ keratomileusis
for moderate to high myopia. A randomized prospective study.
Ophthalmology105:1512-22, discussion1522-3, 1998
22.Steinert RF, Hersh PS : Spherical and aspherical photorefractive
keratectomy and laser in-situ keratomileusis for moderate
to high myopia: two prospective, randomized clinical trials.
Summit technology PRK-LASIK study group. Trans Am Ophthalmol
Soc96:197-221;discussion221-7, 1998
23.el Danasoury MA, el Maghraby A, Klyce SD, Mehrez K :
Comparison of photorefractive keratectomy with excimer laser
in situ keratomileusis in correcting low myopia (from -2.00
to -5.50 diopters). A randomized study. Ophthalmology 106
: 411-20 ;discussion420-1, 1999
24.Lee JB, Kim JS, Choe C, Seong GJ, Kim EK: Comparison
of two procedures:photorefractive keratectomy versus laser
in situ keratomileusis for low to moderate myopia. Jpn J
Ophthalmol45:487-91, 2001
25.Chalmers TC, Smith H Jr, Blackburn B, Silverman B, Schroeder
B, Reitman D, Ambroz A : A method for assessing the quality
of a randomized control trial. Control Clin Trials2:31-49,
1981
26.DerSimonian R, Laird N : Meta-analysis in clinical trials.
Control Clin Trials7:177-88, 1986
27.Egger M, Davey Smith G, Schneider M, Minder C :Bias in
meta-analysis detected by a simple, graphical test. BMJ315:629-34,
1997
28.Begg CB, Mazumdar M : Operating characteristics of a
rank correlation test for publication bias. Biometrics50:1088
-101, 1994
29.El-Maghraby A, Salah T, Waring GO ?, Klyce S, Ibrahim
O:Randomized bilateral comparison of excimer laser in situ
keratomileusis and photorefractive keratectomy for2.50to8.00diopters
of myopia. Ophthalmology106:447-57, 1999
30.Ioannidis JP, Cappelleri JC, Lau J, Skolnik PR, Melville
B, Chalmers TC, Sacks HS:Early or deferred zidovudine therapy
in HIV-infected patients without an AIDS - defining illness.
Ann Intern Med122:856 - 66, 1995
31.Bourque LB, Lynn MJ, Waring GO 3rd, Cartwright C:Spectacle
and contact lens wearing six years after radial keratotomy
in the Prospective Evaluation of Radial Keratotomy Study.
Ophthalmology 101:421-31, 1994
32.Werblin TP:20/20 - - how close must we get? J Refract
Surg13:300-1, 1997
33.Applegate RA, Howland HC : Magnification and visual acuity
in refractive surgery. Arch Ophthalmol111:1335-42, 1993
34.Hersh PS, Steinert RF, Brint SF : Photorefractive keratectomy
versus laser in situ keratomileusis : comparison of optical
side effects. Summit PRK-LASIK Study Group. Ophthalmology107:925-33,
2000
35.Stulting RD, Carr JD, Thompson KP, Waring GO3rd, Wiley
WM, Walker JG:Complications of laser in situ keratomileusis
for the correction of myopia. Ophthalmology106:13-20, 1999
36.Gimbel HV, Penno EE, van Westenbrugge JA, Ferensowicz
M, Furlong MT:Incidence and management of intraoperative
and early postoperative complications in 1000 consecutive
laser in situ keratomileusis cases. Ophthalmology 105 :1839-47;discussion1847-8,
1998
37.Lin RT, Maloney RK : Flap complications associated with
lamellar refractive surgery. Am J Ophthalmol127:129-36,
1999
38.Sterne JA, Gavaghan D, Egger M:Publication and related
bias in meta-analysis : power of statistical tests and prevalence
in the literature. J Clin Epidemiol 53:1119-29, 2000
39.Egger M, Smith GD, Phillips AN : Meta-analysis :principles
and procedures. BMJ 315 : 1533 - 7, 1997
|
