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REFRACTIVE SURGERY Meta-analysis of Pentacam vs. ultrasound pachymetry in central corneal thickness measurement in normal, postLASIK or PRK, and keratoconic or keratoconus-suspect eyes Wenjing Wu & Yan Wang & Lulu Xu Received: 28 June 2013 /Revised: 8 October 2013 /Accepted: 10 October 2013 /Published online: 12 November 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract Background The aim of this meta-analysis is to evaluate the central corneal thickness (CCT) measurement differences between Pentacam (Oculus Inc., Germany) and Ultrasound Pachymetry (USP) in normal (unoperated eyes , myopic and astigmatic eyes without corneal disease or topographic irregularity), after laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK), and keratoconic or keratoconus suspected eyes. We assess whether Pentacam and USP have similar CCT differences in normal, thinner corneas after LASIK or PRK procedures, and kerotoconic or keratoconus suspected eyes. Methods Data sources, including PubMed, Medline, EMBASE, and Cochrane Central Registry of Controlled Trials on the Cochrane Library, were searched to find the relevant studies. Primary outcome measures were CCT measurement between Pentacam and USP. Three groups of eyes were analyzed: normal; LASIK or PRK eyes; and keratoconus suspected or keratoconic eyes. Results Nineteen studies describing 1,908 eyes were enrolled in the normal group. Pentacam results were 1.47 μm ,95 % confidence interval (CI) -2.32 to 5.27, higher than USP without statistically significant difference (P =0.45). Nine studies with total 539 eyes were included in the corneas after LASIK or PRK. The mean difference in the CCT measurement with Pentacam and ultrasound pachymetry was 1.03 μm, with the 95 % CI -3.36 to 5.42, there was no statistically difference (P=0.64). Four studies with a total of 185 eyes were included in the keratoconic eyes or keratoconus-suspect group, however,the mean difference was -6.33 μm (95 % CI -9.17 to-3.49), which was statistically different between Pentacam and ultrasound pachymetry in the CCT measurement (P <0.0001). Conclusions Pentacam offers similar CCT results to ultrasound pachymetry in normal eyes, thinner corneas after LASIK or PRK procedures. However, in keratoconic or keratoconus-suspect eyes, Pentacam slightly underestimates the central corneal thickness than does ultrasound pachymetry, which may result from the difficulty in fixation of keratoconic eyes, misalignment of Pentacam and the variation of ultrasonic velocity due to the histological deformation. Keywords Corneal thickness . Pentacam . Ultrasound pachymetry . Laser in situ keratomileusis . Photorefractive keratectomy . Keratoconus Introduction The measurement of central corneal thickness is essential in ophthalmic practice especially for corneal refractive surgery [1]. CCT measurement not only influences the design of the surgical procedure, especially for high myopia patients with borderline corneal thickness, but also associates with reducing the risk for post-operative complications [ 2] such as keratectasia or keratoconus [3, 4]. Furthermore, corneal thickness is an important parameter for keratoconus and its therapeutic options, i.e., corneal collagen cross-linking (CXL) [5]. Ultrasound pachymetry was the most popular device to measure corneal thickness and was considered as the gold standard prior to the application of optical pachymetry devices [24]. However, ultrasound pachymetry still has some limitations. In the cornea, neither the acoustic impedances W. Wu : Y. Wang (*) : L. Xu Tianjin Eye Hospital& Eye Institute, Tianjin Ophthalmology and Visual Science Key Laboratory, Clinical College of Ophthalmology, Tianjin Medical University, No 4. Gansu RdHeping District Tianjin 300020, China e-mail: [email protected] Graefes Arch Clin Exp Ophthalmol (2014) 252:9199 DOI 10.1007/s00417-013-2502-5
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Page 1: Meta-analysis of Pentacam vs. ultrasound pachymetry in central corneal thickness measurement in normal, post–LASIK or PRK, and keratoconic or keratoconus-suspect eyes

REFRACTIVE SURGERY

Meta-analysis of Pentacam vs. ultrasound pachymetryin central corneal thickness measurement in normal,post–LASIK or PRK, and keratoconicor keratoconus-suspect eyes

Wenjing Wu & Yan Wang & Lulu Xu

Received: 28 June 2013 /Revised: 8 October 2013 /Accepted: 10 October 2013 /Published online: 12 November 2013# Springer-Verlag Berlin Heidelberg 2013

AbstractBackground The aim of this meta-analysis is to evaluate thecentral corneal thickness (CCT) measurement differencesbetween Pentacam (Oculus Inc., Germany) and UltrasoundPachymetry (USP) in normal (unoperated eyes , myopic andastigmatic eyes without corneal disease or topographicirregularity), after laser in situ keratomileusis (LASIK) orphotorefractive keratectomy (PRK), and keratoconic orkeratoconus suspected eyes. We assess whether Pentacamand USP have similar CCT differences in normal, thinnercorneas after LASIK or PRK procedures, and kerotoconic orkeratoconus suspected eyes.Methods Data sources, including PubMed, Medline,EMBASE, and Cochrane Central Registry of ControlledTrials on the Cochrane Library, were searched to find therelevant studies. Primary outcome measures were CCTmeasurement between Pentacam and USP. Three groups ofeyes were analyzed: normal; LASIK or PRK eyes; andkeratoconus suspected or keratoconic eyes.Results Nineteen studies describing 1,908 eyes were enrolledin the normal group. Pentacam results were 1.47 μm ,95 %confidence interval (CI) -2.32 to 5.27, higher than USPwithout statistically significant difference (P =0.45). Ninestudies with total 539 eyes were included in the corneas afterLASIK or PRK. The mean difference in the CCTmeasurement with Pentacam and ultrasound pachymetrywas 1.03 μm, with the 95 % CI −3.36 to 5.42, there was nostatistically difference (P=0.64). Four studies with a total of185 eyes were included in the keratoconic eyes or

keratoconus-suspect group, however,the mean differencewas −6.33 μm (95 % CI −9.17 to-3.49), which wasstatistically different between Pentacam and ultrasoundpachymetry in the CCT measurement (P <0.0001).Conclusions Pentacam offers similar CCT results toultrasound pachymetry in normal eyes, thinner corneas afterLASIK or PRK procedures. However, in keratoconic orkeratoconus-suspect eyes, Pentacam slightly underestimatesthe central corneal thickness than does ultrasound pachymetry,which may result from the difficulty in fixation of keratoconiceyes, misalignment of Pentacam and the variation ofultrasonic velocity due to the histological deformation.

Keywords Corneal thickness . Pentacam . Ultrasoundpachymetry . Laser in situ keratomileusis . Photorefractivekeratectomy . Keratoconus

Introduction

The measurement of central corneal thickness is essential inophthalmic practice especially for corneal refractive surgery[1]. CCT measurement not only influences the design of thesurgical procedure, especially for high myopia patients withborderline corneal thickness, but also associates with reducingthe risk for post-operative complications [2] such askeratectasia or keratoconus [3, 4]. Furthermore, cornealthickness is an important parameter for keratoconus and itstherapeutic options, i.e., corneal collagen cross-linking (CXL)[5].

Ultrasound pachymetry was the most popular device tomeasure corneal thickness and was considered as the goldstandard prior to the application of optical pachymetry devices[2–4]. However, ultrasound pachymetry still has somelimitations. In the cornea, neither the acoustic impedances

W. Wu :Y. Wang (*) : L. XuTianjin Eye Hospital& Eye Institute, Tianjin Ophthalmology andVisual Science Key Laboratory, Clinical College of Ophthalmology,Tianjin Medical University, No 4. Gansu RdHeping DistrictTianjin 300020, Chinae-mail: [email protected]

Graefes Arch Clin Exp Ophthalmol (2014) 252:91–99DOI 10.1007/s00417-013-2502-5

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nor the histological locations of the interfaces are exactlyknown and have to be approximated [6, 7]. In addition, CCTmeasurement can be different in eyes after LASIK or PRKwith increasing corneal hydration , variability of sound speedand reflection interface, and alterations in corneal shaperendering reconstruction algorithms inappropriate [8–10].

In recent years, Pentacam has been widely used astopographic pachymetry, which uses a rotating Scheimpflugcamera to reconstruct the anterior and posterior cornealtopographies from a height [11, 12]. Since Pentacam doesnot depend on reflection of light or sound waves from thecorneal surfaces, it is not supposed to be influenced byscarring or edema [13] which has been shown to affectultrasound pachtmetry [8, 9]. However, previous study hasdemonstrated that [14] greater patient difficulty in fixation andalignment for the operator in cases of keratoconus that couldlead to significant variations in Pentacam data.

A number of previous reports directly compared the CCTresults of these two instruments. Some studies [15–18]suggested that Scheimpflug CCT measurements are alwaysthinner than ultrasound in normal, LASIK or PRK,keratoconus suspected eyes. However, other studies havefound that Pentacam offers a thicker [19–21] or similar [13,22] results. Above all, it is not entirely clear whether Pentacamcould offer as accurate a CCT results as ultrasonic pachymetryin normal eyes, and whether CCT results from the Pentacamcould be used interchangeably with ultrasound for thinnercorneas after LASIK or PRK procedures, and keratoconic orkeratoconus suspected eyes characterised by an ectatic cornealdisorder. In this study, meta-analysis was performed forexisting comparative studies of Pentacam vs. ultrasound forCCT measurement in an attempt to detect any differences innormal eyes, post-LASIK or PRK eyes, and keratoconus orkeratoconus-suspect eyes. To the best of our knowledge, thisis the first meta-analysis of central corneal thicknessmeasurement between Pentacam and ultrasonic pachymetry.

Materials and methods

Reports of clinical trials comparing the central cornealthickness measurements by Pentacam and ultrasoundpachymetry were identified through a systematic search. Thefollowing databases were searched including PubMed,Cochrane Central Register of Controlled Trials on theCochrane Library, MEDLINE, and EMBASE. Searches wererestricted to the English language, for reports publishedbetween January 1, 2003 and April 28, 2013. The keywordswere Pentacam, ultrasound and corneal thickness. Full copiesof all relevant studies were obtained and assessed to determinewhether they met standard quality criteria for inclusion in thestudy. In addition, the reference lists of original reports and

review articles retrieved through the search were reviewed foradditional studies.

Qualitative Assessment and Data Extraction

For each study, the following data were extracted: patient age,number of subjects, the year of publication and location of thetrial. We assessed sources of systematic bias and the quality ofthe trials according to the methods described by Jadad et al.[23]. Two reviewers (Wenjing Wu and Lulu Xu) performedthe data extraction and the methodological quality assessmentof the trials independently. Results were compared, and anydiscrepancies between the reviewers’ results were resolved byconsensus.

Outcome Measures

The measurement results in terms of the central cornealthickness with Pentacam and USP were compared in normaleyes. The differences with Pentacam and ultrasonicpachymetry in post-LASIK and post-PRK eyes were alsocompared since previous studies [9, 18, 24] have shown thatthe absolute magnitude of corneal thickness can influencemean pachymetry values. Patients with keratoconus orkeratoconus suspected were also included since it wasreported that [13] the discrepancy between Pentacam andultrasound pachymetry in measuring the CCT may beincreased in keratoconic corneas due to histopathologyfeatures.

Statistical Analysis

For each comparison and outcome, we undertook a separatemeta-analysis. As the corneal thickness has a continuousvariance, we calculated the weighted mean difference(WMD). Heterogeneity was assessed using the Q test, P <0.01 was considered significant different. The fixed effectsmodel was used to pool the data. If the heterogeneity washigher than 50 %, the random effects model was used topool the data because of the relatively higher difference inclinical characteristics among studies and the variation insample sizes, P <0.05 was considered statisticallysignificant. The statistical analysis was performed by useof RevMan software (version 5.0, Cochrane Collaboration,Oxford, UK).

Results

There were forty-eight trials relevant to the search terms;twenty-four studies were excluded after full text evaluationbecause of French or Chinese languages in the text, or lack ofrelevant data. Of the enrolled 24 publications, fifteen studies

92 Graefes Arch Clin Exp Ophthalmol (2014) 252:91–99

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[13, 15, 16, 19, 22, 25–34] compared the difference in normaleyes. Four studies [17, 21, 35, 36] compared differences ineyes after LASIK, and PRK. Two studies were about thecomparison between normal, after LASIK [20] and PRK eyes[18]. Two studies [16, 37] compared the corneal thicknessmeasurements in normal, after LASIK, and keratoconus-suspected eyes and another study [13] compared the centralcorneal thickness in normal and keratoconic eyes. One study[38] compared the agreement in the CCT measurementbetween Pentacam and ultrasound pachymetry inkeratoconic or keratoconus suspected eyes. The enrolledstudies were presented in Tables 1, 2, 3, which were createdby Microsoft Office 2007 (Microsoft Corporation,Redmond, Washington, USA).

The central corneal thicknesses with Pentacamand Ultrasound pachymetry in normal eyes

The results (Fig. 1) showed CCT with Pentacam andultrasound were similar without significant difference (P=0.45). The mean difference between Pentacam and USP innormal eyes was 1.47 μm with the 95%CI (−2.32, 5.27). Theheterogeneity was I2 =64 % (P <0.0001) although the randomeffect model was used to pool the data, which was higher thanthe normal scale by 50 %.The results were carefullyreexamined to find the source of the heterogeneity. Everystudy was excluded to find changes in heterogeneity, whenthe study of Lee et al. [28] was excluded, the heterogeneitydecreased remarkably to 55 %, the subjects in the study were

Table 1 Characteristics of the included trials evaluating Pentacam and ultrasound pachymetry in CCT measurement in normal eyes

Study/year Country Patients /eyes

Mean age(year)

Gender Instrument

SD/Range M/F Pentacam Ultrasound

O’Donnell, C [15] et al./2005

UK 21/21 29.2±9.8 NG Oculus Inc.,Germany Allergan-Humphrey 850

Barkana, Y [32] et al. /2005 Israel 2424 50.7±17.4 9/15 Oculus Inc., Germany pocket pachymeter, Quantel Medical

Lackner, B [6] et al. 2005 Austria 30/30 31.5±3.8 14/16 Oculus Inc, Wetzlar, Germany SP-2000; Tomey, Nagoya, Japan

Ucakhan O O [13] et al./2006

Turkey 45/45 26.6 ±9.9(13–58)

NG Pentacam CES Oculus, Inc. Micropach 200P Sonomed, Inc.

Kim, S. W [18].et al. /2007 Korea 18/25 28.1±5.7 NG Oculus Inc, Wetzlar, Germany UP-1000; NIDEK, Gamagori, Japan

Al-Mezaine, H. S. [22]et al./2008

SaudiArabia

492984 NG NG Oculus Inc., Germany DGH technology, Inc., San Diego,CA, USA

Prospero P C [16] et al. /2009

Mexico NG/103 NG NG Oculus Inc., Germany Sonogage Corneo-GagePlus,Sonogage Inc

Jahadi, H. H. [25] et al./2010

Iran 47/47 19-37 21/26 Pentacam HR;Oculus UP-1000; NIDEK, Gamagori, Japan

Nam, S. M. [26] et al./2010 Korea 50/50 28.6±4.8 12/40 Oculus, Inc., Wetzlar, Germany Pocket-II; Quantel Medical, Inc.Bozeman,MT

Dilraj S. Grewal [37] et al.2010

USA 50/50 32.6±4.4(25–60)

24/26 Oculus Inc., Wetzlar, Germany Model 200P, Sonomed, Inc

Lee, Y. G. [28] et al./2011 Korea 104/104 62.4±14.1(23–82)

48/56 Oculus Inc, Wetzlar, Germany UP-1000; NIDEK, Gamagori, Japan

Modis, L. J [33] et al./2011 Hungary 46/46 50.5±18 16/30 Pentacam HR; Oculus,Wetzlar,Germany

AL-2000;Tomey, Tennenlohe,Germany

Gonzalez-Perez, J [34]et al./2011

Spain 22/22 21±2 (20–29) 7/15 Oculus Inc, Wetzlar, Germany Paxis, Biovision Inc,Clermont

Ferrand, France

Hashemi, H. [29] et al./2011

Iran 47/47 32±10.4 (19–64)

19/28 Oculus Inc., Germany Nidek,US-1800 ECHOSCAN

Fares, U. [30] et al./2011 UK 40/67 38.65±14.58(19–76)

24/16 Oculus, Inc., Wetzlar, Germany SP 3000, Tomey,Nagoya, Japan

Ishibazawa, A. [27] et al./2011

Japan 30/30 29±7 18/12 Oculus Inc, Wetzlar, Germany SP-2000; Tomey, Nagoya, Japan

Luo, Y. H. [31] et al./2012 China 148/148 24.72±5.35(15–36)

88/60 Oculus Inc, Wetzlar, Germany SP-3000; TomeyTechnology,Nagoya,Japan

Chen, S. [19] et al./2012 China 35/35 23.9 ±2.7(18–29)

21/14 PentacamHR; Oculus, Wetzlar,Germany

SP-3000;Tomey Inc., Nagoya, Japan

Park, S. H. [20] et al. /2012 SouthKorea

30/30 27±7 10/20 Oculus Inc, Wetzlar, Germany Advent; Mentor O&O, Norwell, MA

CCT central corneal thickness, NG not given, SD standard deviation, M male, F female

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found to be older than other studies as themean age was 62.4±14.1 years wherein as others they were always lower than40 years. Another two studies [32, 33] were also excludedsince the mean age was older than 40 years. Studies of Al-Mezaine et al. [22] and Kim et al. [18] were excluded becausethe mean age cannot be found in the text. The heterogeneitydecreased to 26 % after those studies were excluded. Theoverall results (Fig. 2) do not change, which demonstrated thatPentacam showed good agreement with ultrasoundpachymetry.

The central corneal thicknesses with Pentacam and ultrasoundin normal eyes (mean age <40 years old)

The results (Fig. 2) showed that, the CCT results withPentacam and ultrasound were similar without statistical

difference in patients whose mean age was less than 40 yearsold, Pentacam CCT results were 0.40 μm lower than that ofultrasound with the 95% CI (−1.80, 2.60), P=0.72. Thesensitivity analysis was performed by excluding every study,the overall results did not change (P >0.05).

The central corneal thicknesses with Pentacam and ultrasoundin LASIK and PRK eyes

The results (Fig. 3) suggested that Pentacam showed goodagreement with ultrasound in eyes after LASIK or PRK.The mean difference was 1.03 μm with the 95%CIchanged from −3.36 to 5.42, P =0.64. Sensitivity analysiswas performed by excluding the study regarding thecentral corneal thickness measurement difference in PRK

Table 2 Characteristics of the included trials evaluating Pentacam and ultrasound pachymetry in CCT measurement in thinner corneas after LASIK orPRK eyes

Study Country Follow-up Patients/eyes

Mean age Gender Instruments

SD/Range M/F Pentacam Ultrasound

Kim S W [18] et al./2007

Korea 1-3 months 15/24 28.4±6.3 NG Oculus Inc, Wetzlar,Germany

UP-1000; NIDEKGamagori, Japan>4 months 14/21 27.0 ±7.1 NG

Ciolino J B [36] et al./2007

USA 12 months 53/104 38 (22–56) 23/30 Oculus Inc., Wetzlar,Germany

DGH 550 Technology, Inc,Exton, USA

Ho T [17] et al./2007 China 6 months 52/103 NG NG Oculus, Inc Sonomed, 200P

Al-Mezaine H S [22]et al./2008

SaudiArabia

>6 weeks 72/143 NG NG Oculus Inc., Wetzlar,Germany

DGH-1000 Technology, Inc

Prospero, P. C [16]et al./2009

Mexico NG NG/17 NG NG Pentacam Sonogage Corneo-GagePlus, Sonogage Inc

Dilraj S. Grewal [37]et al. 2010

USA 1 year 50/50 29.2±5.6(18–49)

23/27 Oculus Inc., Wetzlar,Germany

Model 200P, Sonomed, Inc

Huang, J [21] et al./2011 China 207.1±151.2 d (30 to720 d)

47/47 23.5±4.3(18–34)

NG Pentacam HR, Oculus SP-3000, Tomey Inc.,Nagoya, Japan

Park, S. H. [20] et al. /2012

SouthKorea

7.51±4.38 months 30/30 28±6 6/24 Oculus, Wetzlar,Germany

Advent; Mentor O&O,Norwell, MA

CCT central corneal thickness, NG not given, SD standard deviation, M male, F = female

Table 3 Characteristics of the included trials evaluating Pentacam and ultrasound pachymetry in CCT measurement in keratoconic or keratoconussuspected eyes

Study/year Country Patients Mean age( year) Gender Instrument

SD/Range M/F Pentacam Ultrasound

Ucakhan O O [13] et al./2006 Turkey 62/62 26.2±9.0 (13–52) NG Pentacam CES Oculus, Inc. Micropach 200P Sonomed, Inc.

de Sanctis U [37] et al./2007 Italy 30/30 37±6 (19–61) 22/11 Pentacam software version 1.14 Allergan-Humphrey 850 Dublin,California, USA

Prospero P C [16] et al. /2009 Mexico NG/40 NG NG Pentacam Sonogage Corneo-Gage Plus,Sonogage Inc

Dilraj S. Grewal [37] et al. 2010 USA 50/50 30.6±3.1 (18–54) 26/24 Oculus Inc., Wetzlar, Germany Model 200P, Sonomed, Inc.

CCT = central corneal thickness; NG = not given; SD = standard deviation; M = male; F = female

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eyes [18]. The overall result was similar without statisticaldifference. (Shown in Fig. 4)

The central corneal thicknesses with Pentacam and ultrasoundin eyes after LASIK

The results (Fig. 4) suggested that Pentacam providedcomparable CCT results with ultrasound in patients afterLASIK. The mean difference was 0.60 μm with the CIchanged from −3.99 to 5.20. The sensitivity analysis wasperformed by excluding the Se-Hoon Park et al., study [20]due to its having compared the difference in post FS-LASIKeyes; the result did not change either(mean difference0.39 μm ,95%CI [−4.39, 5.18], P=0.87).

The central corneal thicknesses in keratoconic or keratoconussuspected eyes

Compared with ultrasound pachymetry, Pentacam measuredCCT significantly thinner than ultrasound pachymetry inkeratoconic or keratoconus suspected eyes. The meandifference was −6.33 μm with the 95%CI (−9.17,-3.49), P <0.0001 (Fig. 5). This may result from the different degree andpatterns of the keratoconus eyes since the severe keratoconuscould lead to a larger difference in the CCT measurement inPentacam compared to ultrasound [13], the cone positioncould lead the corneal apex to be changed remarkably fromcenter to the peripheral part which may cause misalignmentand erroneous CCT results [39]. Furthermore, the distortedcorneal shape in keratoconic eyes could also make it difficult

Fig. 1 The central corneal thicknesses with Pentacam and ultrasound in normal eyes. df = degree of freedom; I2 = extent of inconsistency; Z = overalleffect

Fig. 2 The central corneal thicknesses with Pentacam and ultrasound in normal eyes (mean age <40 years old), df = degree of freedom; I2 = extent ofinconsistency; Z = overall effect

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to determine the real position of the pupil center, contributingto misalignment of the probe which may cause widervariability in these corneas [37]. In addition, thehistopathological changes including irregular and elongatedepithelial cells, altered organization of collagen fibers, andendothelium irregularity in keratoconic corneas may influencethe path of light rays and the velocity of US, leading to aninaccurate measurement [15, 37].

Discussion

To the best of our knowledge, this study was the first meta-analysis to compare Pentacam results with ultrasoundpachymetry in terms of CCT measurement in three groupsincluding normal; after LASIK or PRK eyes; and keratocussuspected or keratoconic eyes. Our study has a greaterstatistical power than that of each study by combining resultsof these trials.

Our study provides evidence that Pentacam could providean accurate central corneal thickness as ultrasoundpachymetry in normal eyes. In addition, the mean difference

became slightly smaller when patients mean age was less than40 years old. Moreover, Pentacam offers similar CCT resultswith small deviation in thinner corneas after LASIK and PRKprocedures, which is not clinically significant to affect theprecise measurement of the CCT for post-LASIK eyesespecially for post-operative patients searching forenhancement [40–42]. In addition, previous studies [17, 43]demonstrated that the presence of dry eye after LASIK, andvariation of ultrasound speed in the post-operative corneas [9]can affect corneal pachymetry. However, our results suggestedthat these factors did not obviously distort corneal imagingand measurements.

With respect to keratoconic or suspected eyes, however,Pentacam underestimated the central corneal thicknesscompared with USP, the mean difference was −6.33 μm withthe 95 % CI (−9.17,-3.49). A previous study [16] has foundthat the mean difference was statistically similar in thekeratoconus suspected group, Ucakhan [13] found thatPentacam and ultrasound had good agreement in mildkeratoconus (K<47 D) with the central corneal thickness478.6±10.5 μm for Pentacam, and 481.9±10.3 μm forultrasound. However, Ucakhan [13] also suggested that in

Fig. 3 The central corneal thicknesses with Pentacam and ultrasound in LASIK and PRK eyes, df = degree of freedom; I2 = extent of inconsistency; Z =overall effect

Fig. 4 The central corneal thicknesses with Pentacam and ultrasound in eyes after LASIK, df = degree of freedom; I2 = extent of inconsistency; Z =overall effect

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moderate keratoconus (47<K<55), Pentacam and ultrasoundshowed a bigger difference; the average central cornealthickness was 433.7±14.7 μm for Pentacam, and 444.2±11.4 μm for ultrasound. Moreover, in severe keratoconiceyes (K>55D), the mean difference became evident, whichwas approximately -27 μm and Pentacam significantlyunderestimate the central corneal thickness (CCT 358.2±19.2 μm for Pentacam, 385.2±14.7 μm for ultrasound).The reasons for underestimation in Pentacam were suspectedto be misalignment in keratoconic eyes especially in advancedkeratoconic eyes with Pentacam. In the temporal cone, inferiorcone, superior cone, and oblique bowtie pattern keratoconus[12], which the corneal apex could change remarkably; it ismore likely to cause misalignment, and result in thecorresponding locations on the corneal reading might notbeing at the corneal center [39] during the operation ofPentacam. With respect to Pentacam, previous study hassuggested that decreased vision [44] and higher levels ofvertical coma, primary coma and coma-like aberrations arepresent in keratoconic eyes compared to normal eyes [45],which could cause greater patient difficulty in seeing andlooking at the red fixation light leading to significantvariations in Pentacam parameters such as Kmax, Rmin(front)and Rmin(back) than in normal or normal postoperativeLASIK corneas [14]. According to the principle of Pentacam,the K value and thickness all are reconstructed by theelevation data [11, 12] ,therefore, the central corneal thicknesswas likely to be erroneously measured with Pentacam inkeratoconic especially advanced keratoconic eyes. In termsof ultrasonic pachymetry, the misalignment can cause thickermeasurement because the cornea is thicker in the peripheralpart than the center. Furthermore, in keratoconic eyes, theoperator may misalign the probe away from the corneal centerto avoid epithelium damage of the cone which is especiallyobvious in the already diagnosed advanced central conekeratoconus because of the awareness of the patientdiscomfort, epithelial damage, and spread of infection withthis contact method. Moreover, previous study [15] hasdemonstrated that in keratoconic eyes, some histopathologyfeatures affecting the optical properties and hydration ofcorneal tissues including irregular epithelial cells, and alteredorganization of collagen fiber could influence the path of light

rays and the velocity of ultrasound, leading to a disturbedmeasurement. Further studies might be needed to investigatethe exact reason for the larger difference in keratoconic eyesbetween Pentacam and ultrasound than normal, post-LASIKand PRK eyes.

One of the purposes of this study was also to showprecautions for evaluating central corneal thickness ofkeratoconic eyes with Pentacam, which are likely to beerroneously underestimated if the slight mean differencesbetween Pentacam and USP of normal, post LASIK andPRK corneas were used to analyze mean differences ofkeratoconic eyes whose difference is actually bigger and havea statically significant difference [46]. Therefore, we suggestthat surgeons should be cautious when interpreting centralcorneal thickness data from Pentacam and ultrasound in eyeswith keratoconus. Some experts suggest that OCT (OpticalCoherence Tomography) could be used to achieve thetopographic data in all problematic eyes in a noninvasivemanner. However, whether OCT could offer as accurate CCTresults as ultrasound pachymetry in normal eyes, with thinnercorneas after LASIK and PRK still need further investigation asprevious studies showed thinner results [47, 48]. The specialtyof corneal pachymetry with OCT in keratoconus-suspected andkeratoconic eyes is also in need of further study [49].

However, several limitations existed in our study. First, wecould only include data from published articles, and it ispossible that bias is introduced if studies with small or reverseeffects exist have not been published. In addition, a problemwith meta-analysis of instruments in evolution as opposed to adrug treatment is that changes in technology and techniquemay impact the results significantly [50]. In the last decade,Pentacam has evolved from basic, classic to Pentacam HR[11] with better precision in pachymetry. With respect toultrasound pachymetry, multiple proprietary platforms areavailable for CCT measurements. Higher frequencyultrasound could offer more accurate corneal thickness thanlow frequency ultrasound. In this study, at least ten types ofultrasound instruments were used for CCT measurement.Further studies might be required to investigate the meandifferences of CCT measurement between Pentacam andultrasound pachymetry in cases of corneal ectasia, scarring,and other corneal refractive procedures.

Fig. 5 The central corneal thicknesses in keratoconic or keratoconus suspected eyes .df = degree of freedom; I2 = extent of inconsistency; Z = overalleffect; USP = ultrasound pachymetry

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In summary, the present study suggests that there are nosignificant differences in the central corneal thicknessmeasurement between Pentacam and ultrasound pachymetryin normal eyes and thinner corneas after LASIK or PRK.Pentacam could offer as accurate a central corneal thicknessas the gold standard ultrasound pachymetry in normal eyesand thinner corneas after LASIK and PRK. However, inkeratoconus suspected and keratoconic eyes, Pentacam couldresult in underestimation of central corneal thicknesscompared with ultrasound pachymetry. Surgeons should beaware that CCT results from these two instruments could notbe used interchangeably in diagnosed keratoconic eyesespecially in advanced keratoconus eyes. Additionaltechniques might be required to find out how to minimizemeasurement bias during the operation of Pentacam andultrasound pachymetry in cases of keratoconic or keratoconussuspected eyes.

Acknowledgments The authors are grateful for the technical support ofTianjin Eye Hospital & Eye Institute, Tianjin Key Lab of Ophthalmologyand Visual Science.

Conflicts of interest and source of funding The authors have nofinancial or proprietary interest in any material or method mentioned.This work has received a National and Science Program Grant(No.81170873), China.

Grants and financial support This work was supported by theNational Natural and Science Program Grant (No. 81170873).

Conflicts of Interest and Source of Funding None of the authors has afinancial or proprietary interest in any material or method mentioned.

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