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were imported into the Endnote software (version X3; Thomson screening, 206 articles identied as duplicated and 256 iden-
Reuters, Philadelphia, PA). tied as unrelated topic were excluded. Another 13 articles
were excluded after applying the exclusion criteria (Fig. 1). The
remaining 13 articles were included in the analysis and sub-
Screening of Articles
sequently classied into 4 groups depending on the treatment
Two independent reviewers assessed the titles and
arms used in each of them (Fig. 1). The techniques used in the
abstracts of all literature records retrieved from online search. control groups were simple excision with bare sclera in 2
Duplicated records and unrelated articles were excluded after
studies,17,18 CAT in 3 studies,1921 intraoperative MMC in
the initial screening. Subsequently, full texts of the relevant
5 studies,1115 and AMT in 3 studies.2224 The Jadad score
records were obtained and a detailed review was performed.
of all included studies ranged from 1 to 3 (Table 1). No
RCTs with primary or recurrent pterygium and LCAG as one statistically signicant heterogeneity was found in any of
of the treatment arms were included for analysis. Exclusion
the groups (all P . 0.05), and a xed-effect model was used
criteria included uncontrolled studies, nonrandomized studies,
in all analysis.
studies using 2 or more advanced techniques, such as LCAG, Two trials by Du et al17 and Fan et al18 reported lower
MMC, or AMT in a single treatment arm, and incomplete
recurrence rates with LCAG as compared with the bare sclera
information from published data. For multiple publications
technique in patients with primary pterygium. The pooled OR
using all or part of the same study population, the most recent was 0.08 (95% CI, 0.040.17, P , 0.00001) (Fig. 2A). The
report was used. A third masked reviewer was consulted
Begg funnel plot did not show any publication bias or asym-
when required to resolve any discrepancy.
metry (Fig. 3A).
Comparison of LCAG and CAT was reported in 3
Data Extraction and Statistical Analysis studies. Of these, subjects with recurrent pterygium were
The quality of each clinical trial was graded using the included in 1 study,19 whereas the other 2 studies included
Jadad score.16 Jadad score is used to independently assess both primary and recurrent pterygia.20,21 The results of these
the methodological quality of a clinical trial. It assesses the studies showed that the recurrence rate of pterygium after
quality of published clinical trialbased methods relevant to LCAG was statistically lower than that after CAT. The pooled
random assignment, double blinding, and the follow up of ORs were 0.11 (95% CI, 0.030.43), 0.03 (95% CI, 0.00
patients. Studies were scored for the presence or absence of 0.72), and 0.10 (95% CI, 0.030.33) in primary, recurrent,
these 3 key methodological recommendations and were and mixed subgroups, respectively, and the overall OR was
awarded 1 point for each recommendation. The data from 0.10 (95% CI, 0.040.23, P , 0.00001) (Fig. 2B). The Begg
each included article were extracted by 2 authors indepen- funnel plot did not show signicant signs of publication bias
dently, including sample size, patient characteristics, details or asymmetry (Fig. 3B).
of intervention, and recurrence. Review Manager Software Five trials compared the outcomes of primary ptery-
(version 5.0.18; The Cochrane Collaboration, Copenhagen, gium excision using LCAG or MMC.1115 Although the
Denmark) was used for statistical analysis. The studies where recurrence rate after LCAG was lower than that after MMC
the surgical technique was the same as that of the control were in all these trials, 3 studies reported ORs that did not reach
grouped and their results were pooled by meta-analysis. statistical signicance.11,13,15 After pooling the results, the over-
Within each meta-analysis, studies were subgrouped accord- all OR was 0.22 (95% CI, 0.090.52, P = 0.0005; Fig. 2C).
ing to the type of pterygia included, whether primary, recur- The Begg funnel plot did not show any publication bias or
rent, or mixed. If the study included both primary and asymmetry (Fig. 3C).
recurrent pterygia and the raw data of each type were avail- The recurrence rate of pterygium after LCAG compared
able, data input was performed into the 2 respective sub- with AMT was reported in 3 RCTs.2224 Cases with recurrent
groups. If the raw data of each group were not available, it pterygium were included in 1 study24 and the other 2 studies
was classied as mixed. Heterogeneity among studies was had both primary and recurrent pterygia, one of which
assessed by the x2 test. Fixed-effect (MantelHaenszel) mod- reported the raw recurrence data of both primary and recur-
els were used unless statistically signicant heterogeneity was rent pterygia.23 Kkerdnmez et al23 reported better cos-
found (P , 0.05). The comparison of recurrence rate between metic success rate when using the CAT than the AMT
2 groups was evaluated using odds ratio (OR) and 95% con- technique. None of the trials reported any signicant differ-
dence interval (CI). The ORs in individual studies were ence between the recurrence rates of LCAG and AMT. The
pooled and depicted using the forest plots. A forest plot is pooled ORs were 0.96 (95% CI, 0.0616.21), 0.84 (95% CI,
a graphical display designed to illustrate the relative strength 0.233.04), and 0.40 (95% CI, 0.072.15) in primary, recur-
of treatment effects in multiple studies addressing the same rent, and mixed subgroups, respectively, and the overall OR
question. A Begg funnel plot was used to quantify the poten- was 0.66 (95% CI, 0.261.70, P = 0.39) (Fig. 2D). The Begg
tial presence of a publication bias. funnel plot did not show signicant sign of publication bias
and asymmetry (Fig. 3D).
RESULTS
A total of 489 articles were retrieved from online DISCUSSION
search, including 144 articles from PubMed, 206 from Pterygium has been classically described as an elastotic
CENTRAL, and 139 from Embase. During the initial degeneration of the conjunctiva. Pterygia are characterized by
TABLE 1. Characteristics of Studies Comparing Pterygium Recurrence Rates After LCAG and Other Surgical Techniques
Jadad Score Group 1 Group 2
Study Randomization Blinded Withdrawal Total P/R Treatment N Recurrence Treatment N Recurrence
17
Du et al 1 0 1 2 P LCAG 112 5 SE 96 41
Fan et al18 1 0 1 2 P LCAG 97 3 SE 98 23
Hu and Gou19 2 0 1 3 R LCAG 53 2 CAT 54 15
Al Fayez20 2 0 1 3 P LCAG 28 0 CAT 22 2
Al Fayez20 2 0 1 3 R LCAG 15 0 CAT 8 4
Cai-Fang et al21 2 0 1 3 P+R LCAG 257 3 CAT 256 27
Sharma et al13 1 0 0 1 P LCAG 20 1 MMC 21 3
Young et al14 1 0 1 2 P LCAG 52 1 MMC 63 10
Biswas et al15 1 0 1 2 P LCAG 30 1 MMC 30 3
Akinci and Zilelioglu11 1 0 0 1 P LCAG 60 2 MMC 52 3
Ari et al12 2 0 1 3 P LCAG 50 2 MMC 50 10
Wei et al22 1 0 0 1 P+R LCAG 57 2 AMT 60 5
Kckerdnmez et al23 2 0 0 2 P LCAG 28 1 AMT 27 1
Kckerdnmez et al23 2 0 0 2 R LCAG 12 2 AMT 11 2
Xia et al24 1 0 0 1 R LCAG 27 3 AMT 30 4
N, number of eyes included; P, primary pterygium; R, recurrent pterygium; SE, simple excision.
FIGURE 2. The forest plots of meta-analysis comparing the recurrence rates of pterygium after LCAG and other techniques. A,
LCAG compared with simple excision. B, LCAG compared with CAT. C, LCAG compared with MMC. D, LCAG compared with AMT.
results showed that the recurrence rates of pterygium after pterygia and with CAT or AMT in both primary and
LCAG were statistically lower compared with those after recurrent pterygia.
simple excision with bare sclera techniques, use of CAT We believe that results of this meta-analysis match the
and MMC. The pooled ORs were 0.08, 0.10, and 0.22 resp- current practice guidelines used for the management of
ectively, with all P , 0.01. In addition, we did not nd any pterygium. However, we could not conclusively demonstrate
statistically signicant difference between the pterygium the efcacy of AMT when compared with LCAG in
recurrence rate after LCAG and AMT. The results of pterygium surgery. This may be attributed to the lack of
LCAG were compared with MMC or bare sclera in primary clinical trials comparing these 2 treatment modalities. The
absence of statistically signicant difference between the In conclusion, we summarized the current evidence for
pterygium recurrence rate after LCAG and AMT as shown in the use of LCAG in pterygium surgery. LCAG results in a lower
the studies included in the present meta-analysis actually rate of pterygium recurrence compared with bare sclera
weakens the rationale of any advantages of the stemness of techniques, CAT and intraoperative MMC application. How-
LCAG, unless the amniotic membrane will be demonstrated ever, we did not nd a statistically signicant difference between
to be able to promote stem cell proliferation. AMT has been the pterygium recurrence rate after LCAG versus AMT. Further
used in pterygium surgery in several other studies to cover large-scale RCTs are needed to determine if there is a difference
large areas of bare sclera after extensive surgical dissection. in pterygium recurrence rate between these 2 techniques.
Recurrence rates between 3.0% and 15% have been reported
using this technique for primary pterygia and between 9.5%
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