Contact Lens & Anterior Eye 37 (2014) 323–330
Contents lists available at ScienceDirect
Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Review
Data extraction and reporting strategies of studies assessing non-central corneal thickness by Pentacam: A review Sven Jonuscheit a,b,∗ a b
Vision Sciences, Department of Life Sciences, Glasgow Caledonian University, UK Anterior Eye Research Group, Institute for Applied Health Research, Glasgow Caledonian University, UK
a r t i c l e
i n f o
Article history: Received 29 November 2013 Received in revised form 23 May 2014 Accepted 4 June 2014 Keywords: Pentacam Non-central corneal thickness Peripheral corneal thickness Data extraction
a b s t r a c t Purpose: To review data extraction strategies for the reporting of non-central corneal thickness with the Pentacam system. Methods: Using predefined search terms, the electronic National Institutes of Health database (PubMed) was searched for studies assessing non-central corneal thickness using the Pentacam instrument. The article titles of the search results were screened for relevance. The abstracts of papers with appropriate titles were retrieved and read. Articles with relevant abstracts were obtained and read in full. The reference list of each article was hand searched to identify further studies. Articles reporting central corneal thickness only were excluded. Results: Seventeen peer-reviewed studies were identified. Considerable differences in data extraction and reporting of non-central corneal thickness were noted, with non-central pachymetry being assessed at locations between 1.5 and 5.0 mm away from the centre. The terminology used to describe non-central pachymetry was inconsistent. Ring-averaged and single point pachymetry data have been reported. Ringaveraged pachymetry may obscure considerable regional variability in corneal thickness. Conclusions: The use of different data extraction and reporting strategies can obscure regional corneal thickness asymmetries. This may influence the monitoring of corneal crosslinking outcomes, the interpretation of corneal swelling in contact lens studies and the clinical decision-making in preoperative assessments of refractive surgery patients. For the reliable identification of regional corneal thickness variations point-pachymetry data appears to be preferable over ring-averaged pachymetry. © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Non-invasive Scheimpflug imaging systems such as the Pentacam (Oculus GmbH, Wetzlar, Germany) provide global pachymetry maps, i.e. corneal thickness (CT) measurements along various corneal meridians. Central (CCT) and non-central corneal thickness (NCCT) are diagnostic parameters used to detect sub-clinical keratoconus in preoperative refractive surgery assessments [1]. NCCT has been considered in corneal crosslinking [2,3] and may provide useful information for corneal surgery at non-central locations such as intra-stromal ring insertion and limbal relaxing incisions [4]. The Pentacam is a non-contact device that uses a monochromatic blue light (475 nm) and a rotating Scheimpflug camera, which revolves 360 degrees around the optical axis, to scan the anterior segment and its main features have been described previously
∗ Correspondence to: Vision Sciences, Department of Life Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK. Tel.: +44 0141 331 3059. E-mail address: [email protected]
[5]. In brief, either 25 or 50 images can be obtained per scan and the procedure takes up to 2 s. Prior to image acquisition, the patient is asked to place their chin onto a chinrest and their forehead against a bar and to fixate on a small round target that is located at the centre of the vertical blue light slit. The instrument is centred on the pupil, using real time monitoring on the instrument’s screen. A second, camera is used to monitor fixation. The scan is usually initiated automatically, but manual acquisition can be selected. Following image acquisition, the observer can view a wide range of topographic maps. A detailed pachymetric map can be obtained by selecting the appropriate option on the Pentacam system. The pachymetry readings are calculated from the spatial difference between anterior and posterior corneal surface, usually perpendicular to the anterior corneal surface (normal-to-surface tangent measurement, personal communication with manufacturer) [6]. These calculations could be considered to approximate radial pachymetry measurements. The maps contain up to 81 single-point numerical pachymetry readings (Fig. 1) and further data points can be obtained by moving the mouse-based cursor over the map. Visual inspection of the colour-coded maps provides a
http://dx.doi.org/10.1016/j.clae.2014.06.004 1367-0484/© 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
324
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
Fig. 1. Numerical and colour-coded point pachymetry map providing 81 numerical data points. The yellow centre indicates lower CT thickness values, whereas cooler colours indicate greater CT. This CT profile, with a notable mid-peripheral and peripheral nasal-temporal CT asymmetry, is representative of a healthy white European individual.
gross overview of any central and non-central abnormalities. Additional features of the Pentacam software include pachymetry at 3 mm from the centre (Fig. 2) and the illustration of the averaged corneal thickness spatial profile as well as the percentage thickness increase from the centre to the periphery near the limbus, both of which are based on pachymetry readings from ring-averaged thickness along 22 imaginary circles that are centred on the thinnest point (Fig. 3, Oculus Pentacam Interpretation Guideline, 2nd ed)
[1]. An advantage of the Pentacam over similar systems is that it can provide non-central pachymetry data up to 5 mm away from the corneal centre, whereas earlier corneal imaging instruments, such as Orbscan, routinely provide data up to 4 and occasionally 4.5 mm away from the centre. Three versions of the Pentacam are currently in clinical use, the Pentacam Basic, Classic, and HR (high resolution). The basic and classic models differ mainly in their software features and the HR model also provides additional hardware updates [5]. While non-contact computerized pachymetry systems are advantageous in reducing inter-observer measurement variability, the complexity of the pachymetry information may present observers with challenges related to the question as to which data should be extracted and compared. For example, observers have the choice between points (Figs. 1 and 2) versus ring-averaged pachymetry (Fig. 3) and will also have to decide from which geographic location to obtain the measurements. The evaluation of peer-reviewed Pentacam studies that report on NCCT confirms that authors have indeed adopted a number of different strategies to extract and report non-central pachymetry measurements. This can be problematic as the use of different data extraction strategies could potentially obscure physiological variations such as changes in pupil size affecting the measurement [7]. Using ring-averaged pachymetry may lead to unexpected results in corneas of generally normal configuration and obscure regional variation in CT. The differences in data extraction and reporting not only make comparisons more difficult, but could potentially affect clinical decision-making, e.g. when assessing the effect of corneal crosslinking outside the corneal centre [2,3]. To date, there has been little discussion regarding different data extraction strategies. The most commonly used methods in previous studies are single-point and ring-averaged data extraction (see below). Some researchers have provided pachymetry for up to 22 0.4 mm increments from the centre [1], others have reported CT measured at a single distance in close proximity to the central cornea, e.g. 1.5 mm away from the centre [8]. The purpose of this paper is to review data extraction strategies used in different studies to report non-central corneal thickness measurements, with a focus on single-point and ring-averaged data obtained with the Pentacam system.
2. Materials and methods
Fig. 2. Numerical and colour-coded pachymetry map providing five data points, one central (apex) and four at nasal, temporal, superior, and inferior locations 3 mm away from the apex.
A literature search was carried out on 15 September 2013 using the United States National Library of Medicine PubMed database. Pre-defined search terms were used individually as well as in combination. The search terms included corneal thickness, peripheral corneal thickness, off-centre corneal thickness, non-central corneal thickness, pachymetry, Pentacam, and Scheimpflug imaging. The abstracts of studies with relevant titles were reviewed to ascertain relevance. All studies with relevant abstracts were retrieved and read in full. The option of ‘Related Publications’ was used to identify further studies. The reference lists of the articles were hand searched for additional relevant titles. Studies were included if non-central pachymetry obtained with the Pentacam system had been considered. From the included studies, data were extracted and entered into a data table (Table 1). Variables retrieved were country in which the study had been carried out, the number of eyes analysed, subject age, the type of central reference point, and the location of the most peripheral non-central corneal thickness reported in the study. NCCT values were obtained and also entered. For the purpose of succinctness, only the most ‘peripheral’, i.e. furthest away from the corneal centre measurement (along the horizontal meridian), was noted. This review focuses on the horizontal meridian, as vertical NCCT measurements are more likely
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
325
Fig. 3. Graphical and tabular illustration of the mean corneal thickness along concentric rings with the thinnest location as the central reference point. The upper graphic shows the progressive increase in absolute corneal thickness from the centre to the periphery (one data point per concentric ring). The lower graphic shows the percentage increase in corneal thickness. The respective ring-averaged pachymetry is given in the table below the graphs.
to be affected by shadows created by the eyelashes as well as the partial lid coverage of the cornea. 3. Results Seventeen relevant Pentacam studies published between 2005 and 2013 were identified. Combined, these studies assessed at least 3008 eyes of 2485 subjects, the age of subjects ranged from 7 to 83 years. The studies included individuals of various ethnic groups and were carried out in Australia [7,9,10], Austria [8], Brazil [1],
China [11–13], France [14], Germany [15,16], Iran [17], Malaysia [18], Mexico/USA [19], Spain [20], and the UK [4,21]. Non-central pachymetry measurements were obtained from corneal locations as close as 1.5 mm [8] to 5 mm away [4,21] from the corneal centre. Some studies included one eye per subject [11–13,16,18,21], whereas other studies analysed two eyes per subject [1,7,8,15,19]. A common data extraction strategy used in a number of studies was the use of ring-averaged NCCT [1,4,9,18,19,21], where pachymetry data along a concentric ring, usually centred on the thinnest location [1] are averaged and presented as a single pachymetry value
326
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
Table 1 Pentacam studies reporting non-central corneal thickness in normal subjects. Only the most peripheral data points reported in each paper are presented in this table. For studies that measured CCT at more than one location, only a single measurement is reported. First author
Year
Country
N
Mean age (years)
Central corneal thickness (mm ± SD)
Non-central corneal thickness (mean ± SD)
Location of most peripheral thickness measurement
Ruefer
2005
Germany
2006
Brazil
44 (range 18–83) Not given
534 ± 36 (A)
Ambrosio
364 eyes of 182 subjects 364 eyes of 196 subjects
609 ± 41 (N) 589 ± 40 (T) 712 ± 50
Buehl
2006
Austria
88 eyes of 44 subjects
24 (range 21–32)
535 ± 33 (ND)
3 mm from centre (right eyes) 8.8 mm ring diameter (4.4. mm radius) centred on thinnest point 1.5 mm from centre (presumably right and left eyes combined)
Lam
2007
China
2007
Germany
Shankar
2008
Australia
23 (range 20–26) 47 (range 18–77) 36 (range 7–65)
558 ± 33 (A)
Khoramnia
39 eyes of 39 subjects 76 eyes of 76 subjects 67 eyes of 35 subjects
Zheng
2008
China
926 eyes of 926 children 662 eyes of 662 adults
Children 12 (range 8–16) Adults 42 (range 30–68)
551 ± 33 (P) 536 ± 29 (P)
642 ± 37 (N) 613 ± 36 (T) 625 ± 35 (N) 606 ± 33 (T)
3 mm from pupil
Bourges Miranda
2009 2009
France UK
30 subjects 23 eyes of 23 subjects
37 27 (range 19–40)
Range 480–614 (ND) 546 ± 5 (SEM) (A)
Not given 803 ± 9 (SEM)
Prospero Ponce
2009
Mexico
597 ± 34
2010
Australia
39 (range 22–66) 27 (range 21–32)
516 ± 32 (ND)
Tyagi
163 eyes of 83 subjects 12 subjects
Within normative range of 475–596
Not given
3 mm from centre 10 mm ring diameter (5 mm radius) centred on thinnest location (first session) 6 mm ring diameter (3 mm radius from centre) 4–8 mm annular corneal region
Gonzales-Perez
2011
Spain
Not given
2012
UK
21 (range 20–29) 39 (range 19–76)
Not given
Fares
22 eyes of 22 subjects 67 eyes of 40 subjects
547 ± 35 (TH)
785 ± 48
Ahmadi Hosseini
2012
Malaysia
25
539 ± 35 (TH)
703 ± 38
Tyagi
2012
Australia
52 eyes of 52 subjects 14 eyes of 14 subjects
28 (range 20–33)
Not given
Ahmadi Hosseini
2013
Iran
No absolute data given, CCT measured over 0–4 mm annular corneal region 535 ± 79 (TH)
Huang
2013
China
50 eyes of 50 subjects 66 eyes of 66 subjects
25 35 (range 18–55)
537 ± 37 (TH)
540 ± 32 (A) 541 ± 37 (P)
539 ± 26 (A)
551 ± 35 (at 3 o’clocka ) 551 ± 34 (at 9 o’clocka ) 617 ± 36 (N) 600 ± 39 (T) 615 ± 34 (N) 599 ± 32 (T) 612 ± 42 612 ± 39
2.5 mm from apex (baseline, first session) 3 mm from centre 3 mm from pupil centre
3 mm radius, averaged from 8 meridians 10 mm ring diameter (5 mm radius from thinnest point) 8 mm ring diameter (4 mm radius from thinnest point) 4–8 mm annular corneal region
645 ± 32
5 mm from thinnest point
606 ± 28 (N) 585 ± 28 (T)
2.5 mm from apex (first reading)
A, apex; N, nasal; ND, central location not defined; P, pupil; T, temporal; TH, thinnest location. a The 3 o’clock position usually refers to the nasal aspect in right eyes, and the 9 o’clock position to the temporal aspect.
for this particular non-central location. Other authors chose to report measurements from individual corneal locations along various corneal meridians, e.g. nasal and temporal [7,11–13,15,16]. 3.1. Non-central pachymetry at 1–2 mm from the centre The terminology used to describe non-central locations varies across different studies. The term ‘peripheral’ has been used to describe pachymetry from as close as 1.5 and as far away as 5 mm from the corneal centre. Buehl and colleagues assessed ‘peripheral’ pachymetry in 88 eyes of 44 subjects aged between 21 and 32 years at a location 1.5 mm away from the corneal centre [8]. Even though these measurements have been described as being ‘peripheral’, it could be argued that the term refers to locations further away from the corneal centre, i.e. closer to the limbus. Unsurprisingly, the NCCT measurements obtained at the 1.5 mm locations were only slightly different from those at the centre (mean CCT 534 m versus PCT 551 m at nasal and temporal locations). Lam and Chen studied NCCT as part of a variability study [11]. The study included 39 eyes of 39 healthy Chinese subjects aged
20–26 years and corneal thickness was measured at 1.5 and 2.5 mm away from the corneal apex. Nasally, the mean NCCT at the 2.5 mm location was 617 m and temporally 600 m. Huang et al. examined central and mid-peripheral CT in a study that compared three rotating Scheimpflug topography systems including Pentacam [13]. Measurements were obtained from 66 eyes of 66 Chinese individuals aged 18–55 years. The NCCT measurements were obtained from locations up to 2.5 mm away from the apex. CCT, nasal, and temporal NCCT were 539 m, 606 m, and 585 m, respectively, indicating a 12% (nasal) and a 9% (temporal) increase in CT for the nasal and temporal locations as compared to the apex. Even though the maximum distance given in the methods-section is 2.5 mm from the apex, the results were labelled CT5mm , a notation that presumably refers to the ringaveraged notation also described in this review. Such notations may cause misunderstandings, as the reader may interpret this as measurements obtained at true 5 mm locations near the limbus. Measurements at 5 mm locations would likely be greater than those obtained at 2.5 mm and the percentage thickness difference would also be greater.
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
3.2. Non-central pachymetry at 3 mm from the centre Several research groups have assessed pachymetry at locations about 3 mm outside the corneal centre, for example in Germany [15,16], Australia [7], China [12], France [14], and Spain [20]. In one of the earliest Pentacam studies, Rüfer and colleagues assessed 364 eyes of 182 subjects aged 18–83 years at the ‘periphery’ 3 mm away from the corneal centre [15]. NCCT was 609 m (nasal) and 589 m (temporal) and therefore about 14% and 10% greater than the mean CCT of 534 m. Khoramnia et al. observed similar NCCT values of 615 and 599 m (nasal and temporal, respectively) in 76 eyes of 76 subjects aged 18–77 years [16]. The NCCT at those two locations was 14% and 11% thicker than CCT, respectively. In Australia, Shankar reported CCT and NCCT of 67 eyes of 35 healthy subjects aged 7–65 years as part of an instrument reliability study [7]. Three eyes were excluded due to the instrument providing a warning on the system’s ‘examination quality specification’. This warning flags up scans that could have been affected by loss of fixation, blinking, or poor instrument centration. The authors provide a valuable description of the Pentacam’s capacity to measure and report corneal thickness and highlight the instrument’s ability to provide CT from limbus to limbus. Shankar and co-authors also point out that the default NCCT location is set to 3 mm away from the pupil centre, but that NCCT is available for virtually all corneal locations by moving the cursor over the pachymetry map. The mean CCT was 541 m for both, pupil centre and corneal vertex CCT. Interestingly, the NCCT at 3 mm was identical for both nasal and temporal locations (612 m) when the pupil centre was used as the reference point. Using the corneal vertex as the central reference point provided a slightly different NCCT of 616 and 612 m for nasal and temporal aspects, respectively. Even though this difference is small, it illustrates that any nasal-temporal CT asymmetry could be dependent on the type of central reference point that is used. The authors note the effect of the pupil diameter variability and pupil decentration on NCCT during repeated measurements and recommend use of the corneal apex rather than the pupil centre as the central reference location for non-central pachymetry measurements by Pentacam. Zheng et al. studied NCCT 3 mm in a large population-based twin study [12]. The mean nasal NCCT was 625 and 642 m for adults and children, respectively. The mean corresponding temporal NCCT was considerably lower at 606 and 613 m for the two study group, respectively. Bourges and colleagues assessed the reliability of the Pentacam in comparison to a scanning slit topography system and ultrasound pachymetry and measured ‘peripheral’ CT of 30 healthy subjects with a mean age of 37 years 3 mm away from the corneal centre, using what was termed the ‘Oculus 3-D matrix files’ [14]. A special feature of this study was the generation of three-dimensional average pachymetry maps. These colour-coded pachymetry models allow for a more intuitive measurement comparison. The CCT ranged from 480 to 614 m, but is not clear whether these data were obtained with the Pentacam or one of the other instruments used in the study. While the inter-instrument differences are described in detail, absolute non-central pachymetry data were not provided. Prospero-Ponce et al. examined NCCT using ring-averaged data (6 mm diameter) as part of a comparative study of healthy individuals, keratoconus suspects, and post-LASIK patients [19]. NCCT was assessed in 163 eyes of 83 subjects (age 22–66 years), 103 of these eyes were healthy and had not undergone surgery. The ring-averaged NCCT was 597 m. Gonzales-Perez and colleagues assessed ‘peripheral’ corneal thickness up to 3 mm from the centre and along eight meridians as part of an instrument comparison study between Pentacam and
327
Orbscan II [20]. The study included 22 eyes of 22 healthy subjects aged 20–29 years. The authors describe the level of agreement between the two imaging systems, but absolute CT data were not included. 3.3. Non-central pachymetry beyond 3 mm from the centre Few studies have reported Pentacam pachymetry for locations beyond 3 mm from the centre [1,4,9,18,21]. In a study on the corneal spatial profile and volume distribution for the differentiation between normal and keratoconic eyes, Ambrosio and colleagues assessed 364 eyes of 196 normal patients in Brazil [1]. NCCT was determined for concentric 22 circles (0.4 mm steps apart) centred on the thinnest point. At the most peripheral location, on a circle of 8.8 mm diameter (corresponding radius 4.4 mm), the ring-averaged NCCT was 712 m, and the mean thinnest CT was 537 m. The percentage CT increases in from the thinnest location to the 8.8 mm circle averaged 33%. Tyagi and colleagues evaluated regional corneal thickness variations in 12 young subjects aged 21–32 to examine the effect of contact lens wear on corneal thickness [9]. In this study, NCCT was assessed at mid-peripheral (4 mm diameter) and peripheral (8 mm diameter) annular regions. Ahmadi-Hosseini et al. assessed 52 eyes of 52 patients in Malaysia in a study to describe the CT distribution and to discriminate between normal and ectatic corneas [18]. The mean ring-averaged peripheral thickness for locations of up to 8 mm diameter (4 mm radius from centre) averaged 703 m. With a percentage thickness increase of 29%. The most peripheral CT measurement provided on the numerical pachymetry maps available from the Pentacam system is for locations close to the limbus 5 mm away from the corneal centre. Fares and colleagues assessed NCCT using two different strategies, namely (i) single point pachymetry measurements at 3 and 7 mm from the apex (radius 1.5 and 3.5, respectively) and (ii) ringaveraged measurements for locations up to 10 mm (5 mm radius) where the concentric circles were centred on the thinnest location [4]. The principal aim of the study was to assess the correlation between central and peripheral CT and to examine whether central pachymetry measurements could be considered sufficient on their own, i.e. without consideration of NCCT. The ring-averaged NCCT at the most peripheral location was 785 m, which corresponds to a 43% increase. As part of a Pentacam repeatability study, Miranda and colleagues assessed 23 eyes of 23 subjects with a mean age of 27 years [21]. Peripheral ring-averaged pachymetry of up to 10 mm diameter centred on the thinnest location was obtained and averaged 803 m for this most peripheral location. In their study the authors point out that the increased variability of peripheral CT measurements may be associated with regional corneal asymmetries in CT, which could be interpreted as an argument for the reporting of point- rather than ring-averaged pachymetry. In a study that aimed to examine corneal swelling in response to rigid contact lens wear, Tyagi and coworkers used data from an annular region 4–8 mm away from the corneal centre [10]. Very recently, Ahmadi Hosseini and colleagues reported NCCT for locations up to 5 mm away from the thinnest point with a mean of 645 ± 32 m [17]. These data were obtained from a normal cohort and NCCT at 5 mm was substantially lower than that of a 4 mm location reported in an earlier study by the same lead author (703 ± 38 m), even though they were obtained further away from the centre [18]. 4. Discussion This review discusses approaches that have been adopted for the reporting of non-central pachymetry obtained with the
328
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
Fig. 4. Illustration of two successive Pentacam scans. The data represent mid-peripheral corneal thickness (3 mm) at the four main meridians (superior, nasal, inferior, and temporal) as reported by Shankar et al. [7]. Reporting point-pachymetry from various meridians indicates differences in the measurements. Averaging the four mid-peripheral values for each scan would provide similar mean thickness values, thereby obscuring any existing differences.
Pentacam system. A main difference between studies was the use of either point-pachymetry from a defined location and ring-averaged pachymetry.
mean CT of 823 m nasally and 772 m temporally was observed. Ring-averaging measurements would obscure deviations from the normal corneal configuration, of which the nasal-temporal NCCT asymmetry is frequently a typical characteristic.
4.1. Clinical relevance of peripheral pachymetry Pachymetry measurements outside of the corneal centre have been used in a number of studies investigating abnormal corneal structure as well as in pre- and postoperative assessments of surgical interventions and have been shown to provide valuable clinical information. Pentacam pachymetry maps have been used for the differentiation of normal thin from ectatic corneas [1]. Central and non-central pachymetry can be used to differentiate between mild to moderate keratoconus and candidates suitable for photorefractive keratectomy [17], to determine corneas outside the normal corneal thickness range, for example in assessments of contact lens-related changes [10]. Relative peripheral pachymetry can be useful in the clinical classification of Fuchs’ endothelial dystrophy [22]. Peripheral Pentacam pachymetry has been utilized in preand postoperative assessments of deep anterior lamellar keratoplasty [23], to evaluate the peripheral edges of the donor button in Descemet’s Stripping Automated Endothelial Keratoplasty, as well as in the subsequent monitoring of postoperative progressive peripheral graft thinning [24]. The Pentacam instrument provides posterior corneal elevation analysis and such assessments have been used to evaluate the mid-peripheral and peripheral cornea after laser refractive surgery for myopia and myopic astigmatism [25]. Peripheral assessments have also been made in the management of post-LASIK ectasia [26]. A number of studies have reported NCCT using ring-averaged data [1,4,9,18,19,21]. This approach provides a single pachymetry reading for points on a circle at a given distance from a central reference point (covering various radial meridians). The advantage of this modality is the use of just a single figure, which is easy to interpret. A disadvantage of reporting ring-averaged pachymetry is that it does not reflect regional intracorneal asymmetries. A recent study carried out at Glasgow Caledonian University in collaboration with the University of Valladolid confirmed a substantial nasal-temporal asymmetry in CT [27]. The magnitude of this asymmetry increased progressively from to the centre towards the limbus, with nasal readings being consistently greater than the corresponding temporal readings. At the most peripheral location (5 mm from centre), a
4.2. Examples of the impact of ring-averaging data on the interpretation of pachymetry Regional structural differences of the cornea have been shown to influence the effect of corneal crosslinking [3], in that crosslinking will be relatively less effective at corneal locations of greater thickness than compared to those of lower thickness (i.e. corneal crosslinking may be relatively less effective nasally than temporally). The treatment effect of corneal crosslinking is reduced by about a third to approximately 65% at 3 mm away from the centre [3]. Interpolation of the treatment results to other corneal locations needs to take into account regional asymmetries, as the nasal peripheral cornea is usually thicker than the temporal periphery [28]. However, these regional asymmetries are obscured if, for example, ring-averaged data were reported, making estimates of effectiveness of treatment more difficult [18,19,21]. A second example of the disadvantage of using ring-averaged data is related to potential problems associated with increased CT variability due to changes in pupil size [7]. The magnitude of these effects may be substantial enough to warrant clinical significance. The sketches in Fig. 4 illustrate two consecutive Pentacam scans and the data shown are as presented in a paper by Shankar and colleagues [7], representing central and mid-peripheral (3 mm) pachymetry. The data are presented as point data for each of the four principal meridians. If one were to use the ring-averaging approach, by which the four mid-peripheral readings are averaged to obtain a single reading for the 3 mm location, the mean mid-peripheral corneal thickness would average 613 m for scan 1 (Fig. 4A) and 611 m for scan 2 (Fig. 4B), thereby indicating no substantial difference between the two images if only ring-averaged date were considered. Analysis of each individual meridian, however, reveals that the change in pupil size in this example has led to a different pachymetry reading with an underestimation of corneal thickness of −28 m temporally and an overestimation of +28 m nasally. These differences would have been obscured if ring-averaged pachymetry had been applied. The reporting of data from the principal meridians, e.g. nasal, temporal, superior,
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
and inferior provides an opportunity to identify changes in pupil diameter more easily. A third example where using ring-averaged data could lead to uncertainty is the comparison of two Pentacam studies. In these studies, pachymetry was obtained from two samples of participants, one in Malaysia and one in Iran. These two studies included a similar number of subjects of similar average age and with similar CCT. One study used ring-averaged data from 5 mm locations (mean ± SD 645 ± 32 m) [17], which were on average considerably lower than the pachymetry values for 4 mm locations in the second study (703 ± 38 m) [18]. NCCT in the study using the more peripheral 5 mm location was considerably lower than the data reported for a 4 mm location. While CT at 5 mm could be expected to be greater than 4 mm from the central reference point, the 4 mm pachymetry data were on average 63 m or approximately 10% greater than the 5 mm data. A possible reason for this discrepancy could be that the two samples display considerable inherent differences, e.g. due to their ethnic background. However, the reason for the finding cannot be ascertained without the knowledge of meridional data. 4.3. Further issues related to non-central pachymetry Previous studies show that the term ‘peripheral’ can be used in several ways. The term ‘peripheral’ has been used to describe corneal thickness measurements outside the corneal centre and has been applied to corneal locations as close as 1.5 mm [8] as well as up to 5 mm from the corneal centre [4]. Not all of these locations can truly be considered to be ‘peripheral’. Non-central pachymetry data from just 1.5 mm outside the centre are likely to differ substantially from readings that were obtained 5 mm away from the centre. Using a more differentiated terminology may be beneficial, i.e. the term ‘peripheral’ could perhaps be restricted to measurements obtained at least 4 mm away from the corneal centre. Measurements obtained between 1.5 and 3.5 mm could be classed as ‘mid-peripheral’ or ‘para-central’, as has been used in a previous study [20]. Any measurements within the central 3 mm (1.5 mm radius) could be classed as ‘central’. Given that corneal thickness increases progressively and asymmetrically from the centre to the limbus, it could be beneficial to agree on more clearly defined terminology for corneal locations. In addition to NCCT, the Pentacam system provides up to three central pachymetric reference points, namely (i) pupil centre, (ii) apex, and (iii) thinnest point pachymetry. The pupil centre is defined as the geometrical centre point of pupil. According to the information provided in the Pentacam instruction manual (version G/70700/1105/e), the apex can be interpreted as the central location at which there is no deviation on either the x- or the y-axis of the anterior surface. The thinnest point is a location that is commonly found slightly off-centre in the inferior-temporal quadrant, but thinnest point pachymetry does not differ significantly from corneal apex thickness [4]. The age range in the studies included in this review varied considerably. As peripheral corneal thickness is inversely associated with age [22,28], interpretation of NCCT should ideally consider the relative age-dependent decline. This is likely to be of greater importance when considering pachymetry readings that are obtained from locations close to the limbus, where the age-related effect is most pronounced. The most advanced Pentacam model, the Pentacam HR provides the user with a number of additional features such as an improved optical design, a 1.45-megapixel camera, and enhanced fixation options [5,29]. With the HR model it is possible to obtain five times the number of data points as compared to the standard Pentacam. While more data points do not necessarily lead to a higher reliability of measurements, the HR model has been
329
reported to provide improved precision of CCT measurements. Corneal apex pachymetry showed the best repeatability (reported as within subject standard deviation) when the cornea fine scan was used (3.15 m), and only marginally poorer repeatability when the 25 pictures scan was used (3.74 m). Peripheral pachymetric repeatability assessed at 4 mm inferiorly was best with the fine scan (7.86 m), and similar when the 25 (8.69 m) or the 50 picture scan (8.24 m) were used. In this reliability study, the authors suggest that the good repeatability of the Pentacam HR could be associated with improvements of the instrument over the standard Pentacam [29]. A previous study that evaluated the reliability of the standard Pentacam showed that the repeatability of pachymetry at the corneal apex was good (−1.04 ± 7.17 m, mean difference ± SD). The study also highlighted a potential problem, namely that the pupil centre is variable and that this variability has an effect on peripheral pachymetry measurements, as repeated peripheral measurement points do not correspond, due to differences in the location of the pupil centre. This effect can be overcome by using the corneal apex as the central reference point, which provided satisfactory peripheral reliability (9.01 ± 8.34 m, mean difference ± SD at three millimetres inferiorly from the corneal apex) [7]. From these studies it can be concluded that, based on the standard deviation between repeated measurements, the Pentacam and the Pentacam HR models provide a comparable reliability of central and peripheral pachymetry measurements. A recent study has investigated the advantage of measuring NCCT by examining the relationship between central and noncentral CT to determine if reliance on central measurements should suffice [4]. The reasoning was that if central and peripheral CT were closely related, this could perhaps eliminate the need to obtain NCCT readings. The study showed a statistically significant correlation between central and non-central CT at locations of up to 5 mm away from the centre (r ≥ 0.635; p < 0.001). Even though approximately 47% of corneal thickness at the 7 mm location could be predicted by CCT, more than 50% of the variability could not be predicted. It was concluded that for most purposes CCT can guide the prediction of NCCT. With contemporary corneal imaging becoming more widely available and NCCT measurements being of potential additional benefit in surgical procedures affecting the mid-peripheral and peripheral corneal zones, e.g. intracorneal ring insertion and limbal relaxing incisions, it could be argued that NCCT should not be neglected. This review seeks to illustrate commonly used approaches to report Pentacam pachymetry. It is hoped that this paper will stimulate and contribute to a discussion as to which strategy is likely to be the most effective for the reporting of non-central pachymetry. This review does not aim to disconsider in any way the methods mentioned in this article, but simply intends to highlight some of the benefits and disadvantages of methods currently used to report Pentacam pachymetry. Further studies would be useful to confirm the clinical importance of the regional differences and asymmetries in corneal thickness. If such regional differences are considered important (indicated by the increasing number of studies reporting such data) then ring-averaged data should be used cautiously. 4.4. How can a more reliable comparison of pachymetry be achieved? Thinnest point data and the measures resulting from concentric ring centred on the thinnest location may be the most appropriate in the detection and classification of keratoconus. However, the assessment of regional variations in corneal thickness could be enhanced by reporting data from at least four meridians. The horizontal meridian is least likely to be affected by partial lid coverage.
330
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
Alternatively, the presentation of a pachymetry map may be even more informative. It is acknowledged that map interpretation requires more time, which may limit its utility in a busy clinic environment. From the examples provided above it can be concluded that point-pachymetry would allow for detection of any substantial regional asymmetries while being easy to obtain and interpret. Regional variations in CT between samples as well as possible effects of physiological changes such as pupil size are easily recognizable. In conclusion, the Pentacam system provides a range of options for the reporting of CT data. Pachymetry measurements can be obtained from locations up to 5 mm away from the corneal centre. As has been illustrated above, different strategies have been used in peer-reviewed articles to report non-central pachymetry data. For some clinical applications, ring-averaged pachymetry may be sufficient. For detailed assessments of regional asymmetries such as the nasal-temporal asymmetry the consideration of single-point pachymetry data along the principal meridians may allow for a more reliable assessment. Funding This work was supported by Santander Universities Fund UK. Conflict of interest The author declares no conflict of interest. Acknowledgements The author would like to thank the reviewers for their constructive comments and support in improving the manuscript. The author also thanks Peter Rafferty, Graeme Kennedy, Andreas Steinmueller, and Sven Reisdorf for helpful discussions on optical aspects of the Pentacam. References [1] Ambrósio Jr R, Alonso RS, Luz A, Coca Velarde LG. Corneal-thickness spatial profile and corneal-volume distribution: tomographic indices to detect keratoconus. J Cataract Refract Surg 2006;32:1851–9. [2] Rehnman JB, Janbaz CC, Behndig A, Lindén C. Spatial distribution of corneal light scattering after corneal collagen crosslinking. J Cataract Refract Surg 2011;37:1939–44. [3] Koller T, Schumacher S, Fankhauser F, Seiler T. Riboflavin/ultraviolet a crosslinking of the paracentral cornea. Cornea 2013;32:165–8. [4] Fares U, Otri AM, Al-Aqaba MA, Dua HS. Correlation of central and peripheral corneal thickness in healthy corneas. Cont Lens Anterior Eye 2012;35: 39–45. [5] Oliveira CM, Ribeiro C, Franco S. Corneal imaging with slit-scanning and Scheimpflug imaging techniques. Clin Exp Optom 2011;94:33–42. [6] Villavicencio O, Belin MW, Ambrósio R, Steinmueller A. Corneal pachymetry: new ways to look at an old measurement. J Cataract Refract Surg 2014;40:695–701.
[7] Shankar H, Taranath D, Santhirathelagan CT, Pesudovs K. Anterior segment biometry with the Pentacam: comprehensive assessment of repeatability of automated measurements. J Cataract Refract Surg 2008;34:103–13. [8] Buehl W, Stojanac D, Sacu S, Drexler W, Findl O. Comparison of three methods of measuring corneal thickness and anterior chamber depth. Am J Ophthalmol 2006;141:7–12. [9] Tyagi G, Collins M, Read S, Davis B. Regional changes in corneal thickness and shape with soft contact lenses. Optom Vis Sci 2010;87:567–75. [10] Tyagi G, Collins MJ, Read SA, Davis BA. Corneal changes following short-term rigid contact lens wear. Cont Lens Anterior Eye 2012;35:129–36. [11] Lam AKC, Chen D. Pentacam pachometry: comparison with non-contact specular microscopy on the central cornea and inter-session repeatability on the peripheral cornea. Clin Exp Optom 2007;90:108–14. [12] Zheng Y, Huang G, Huang W, He M. Distribution of central and peripheral corneal thickness in Chinese children and adults: the Guangzhou twin eye study. Cornea 2008;27:776–81. [13] Huang J, Ding X, Savini G, Pan C, Feng Y, Cheng D, et al. A comparison between Scheimpflug imaging and optical coherence tomography in measuring corneal thickness. Ophthalmology 2013;120:1951–8. [14] Bourges JL, Alfonsi N, Laliberté JF, Chagnon M, Renard G, Legeais JM, et al. Average 3-dimensional models for the comparison of Orbscan II and Pentacam pachymetry maps in normal corneas. Ophthalmology 2009;116:2064–71. [15] Rüfer F, Schröder A, Arvani M-K, Erb C. Central and peripheral corneal pachymetry – standard evaluation with the Pentacam system. Klin Monatsbl Augenheilkd 2005;222:117–22. [16] Khoramnia R, Rabsilber TM, Auffarth GU. Central and peripheral pachymetry measurements according to age using the Pentacam rotating Scheimpflug camera. J Cataract Refract Surg 2007;33:830–6. [17] Ahmadi Hosseini SM, Abolbashari F, Niyazmand H, Sedaghat MR. Efficacy of corneal tomography parameters and biomechanical characteristic in keratoconus detection. Cont Lens Anterior Eye 2013;37:26–30. [18] Ahmadi Hosseini SM, Mohidin N, Abolbashari F, Mohd-Ali B, Santhirathelagan CT. Corneal thickness and volume in subclinical and clinical keratoconus. Int Ophthalmol 2012;33:139–45. [19] Prospero Ponce CM, Rocha KM, Smith SD, Krueger RR. Central and peripheral corneal thickness measured with optical coherence tomography, Scheimpflug imaging, and ultrasound pachymetry in normal, keratoconus-suspect, and post-laser in situ keratomileusis eyes. J Cataract Refract Surg 2009;35:1055–62. [20] González-Pérez J, Gonzalez-Meijome JM, Rodríguez Ares MT, Parafita MA. Topographic paracentral corneal thickness with Pentacam and Orbscan: effect of acoustic factor. Eye Contact Lens 2011;37:348–53. [21] Miranda MA, Radhakrishnan H, O’Donnell C. Repeatability of corneal thickness measured using an Oculus Pentacam. Optom Vis Sci 2009;86:266–72. [22] Repp DJ, Hodge DO, Baratz KH, McLaren JW, Patel SV. Fuchs’ endothelial corneal dystrophy. Ophthalmology 2013;120:687–94. [23] Riss S, Heindl LM, Bachmann BO, Kruse FE, Cursiefen C. Pentacam-based big bubble deep anterior lamellar keratoplasty in patients with keratoconus. Cornea 2012;31:627–32. [24] Scorcia V, Matteoni S, Scorcia GB, Scorcia G, Busin M. Pentacam assessment of posterior lamellar grafts to explain hyperopization after Descemet’s stripping automated endothelial keratoplasty. Ophthalmology 2009;116:1651–5. [25] Zhang L, Wang Y. The shape of posterior corneal surface in normal, post-LASIK, and post-epi-LASIK eyes. Invest Ophthalmol Vis Sci 2010;51:3468–75. [26] Kanellopoulos AJ, Binder PS. Management of corneal ectasia after LASIK with combined, same-day, topography-guided partial transepithelial PRK and collagen cross-linking: the Athens protocol. J Refract Surg 2010;27:323–31. [27] Jonuscheit S, Doughty MJ, Martin R, Rio San Cristobal A, Mackintosh L, MacTaggart D, et al. Body mass index, peripheral corneal thickness and anterior chamber depth in young European adults – a pilot study. ARVO Meet Abstr 2013;54:524. [28] Jonuscheit S, Doughty MJ. Evidence for a relative thinning of the peripheral cornea with age in white European subjects. Invest Ophthalmol Vis Sci 2009;50:4121–8. [29] McAlinden C, Khadka J, Pesudovs K. A comprehensive evaluation of the precision (repeatability and reproducibility) of the Oculus Pentacam HR. Invest Ophthalmol Vis Sci 2011;52:7731–7.
Contents lists available at ScienceDirect
Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Review
Data extraction and reporting strategies of studies assessing non-central corneal thickness by Pentacam: A review Sven Jonuscheit a,b,∗ a b
Vision Sciences, Department of Life Sciences, Glasgow Caledonian University, UK Anterior Eye Research Group, Institute for Applied Health Research, Glasgow Caledonian University, UK
a r t i c l e
i n f o
Article history: Received 29 November 2013 Received in revised form 23 May 2014 Accepted 4 June 2014 Keywords: Pentacam Non-central corneal thickness Peripheral corneal thickness Data extraction
a b s t r a c t Purpose: To review data extraction strategies for the reporting of non-central corneal thickness with the Pentacam system. Methods: Using predefined search terms, the electronic National Institutes of Health database (PubMed) was searched for studies assessing non-central corneal thickness using the Pentacam instrument. The article titles of the search results were screened for relevance. The abstracts of papers with appropriate titles were retrieved and read. Articles with relevant abstracts were obtained and read in full. The reference list of each article was hand searched to identify further studies. Articles reporting central corneal thickness only were excluded. Results: Seventeen peer-reviewed studies were identified. Considerable differences in data extraction and reporting of non-central corneal thickness were noted, with non-central pachymetry being assessed at locations between 1.5 and 5.0 mm away from the centre. The terminology used to describe non-central pachymetry was inconsistent. Ring-averaged and single point pachymetry data have been reported. Ringaveraged pachymetry may obscure considerable regional variability in corneal thickness. Conclusions: The use of different data extraction and reporting strategies can obscure regional corneal thickness asymmetries. This may influence the monitoring of corneal crosslinking outcomes, the interpretation of corneal swelling in contact lens studies and the clinical decision-making in preoperative assessments of refractive surgery patients. For the reliable identification of regional corneal thickness variations point-pachymetry data appears to be preferable over ring-averaged pachymetry. © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Non-invasive Scheimpflug imaging systems such as the Pentacam (Oculus GmbH, Wetzlar, Germany) provide global pachymetry maps, i.e. corneal thickness (CT) measurements along various corneal meridians. Central (CCT) and non-central corneal thickness (NCCT) are diagnostic parameters used to detect sub-clinical keratoconus in preoperative refractive surgery assessments [1]. NCCT has been considered in corneal crosslinking [2,3] and may provide useful information for corneal surgery at non-central locations such as intra-stromal ring insertion and limbal relaxing incisions [4]. The Pentacam is a non-contact device that uses a monochromatic blue light (475 nm) and a rotating Scheimpflug camera, which revolves 360 degrees around the optical axis, to scan the anterior segment and its main features have been described previously
∗ Correspondence to: Vision Sciences, Department of Life Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK. Tel.: +44 0141 331 3059. E-mail address: [email protected]
[5]. In brief, either 25 or 50 images can be obtained per scan and the procedure takes up to 2 s. Prior to image acquisition, the patient is asked to place their chin onto a chinrest and their forehead against a bar and to fixate on a small round target that is located at the centre of the vertical blue light slit. The instrument is centred on the pupil, using real time monitoring on the instrument’s screen. A second, camera is used to monitor fixation. The scan is usually initiated automatically, but manual acquisition can be selected. Following image acquisition, the observer can view a wide range of topographic maps. A detailed pachymetric map can be obtained by selecting the appropriate option on the Pentacam system. The pachymetry readings are calculated from the spatial difference between anterior and posterior corneal surface, usually perpendicular to the anterior corneal surface (normal-to-surface tangent measurement, personal communication with manufacturer) [6]. These calculations could be considered to approximate radial pachymetry measurements. The maps contain up to 81 single-point numerical pachymetry readings (Fig. 1) and further data points can be obtained by moving the mouse-based cursor over the map. Visual inspection of the colour-coded maps provides a
http://dx.doi.org/10.1016/j.clae.2014.06.004 1367-0484/© 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
324
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
Fig. 1. Numerical and colour-coded point pachymetry map providing 81 numerical data points. The yellow centre indicates lower CT thickness values, whereas cooler colours indicate greater CT. This CT profile, with a notable mid-peripheral and peripheral nasal-temporal CT asymmetry, is representative of a healthy white European individual.
gross overview of any central and non-central abnormalities. Additional features of the Pentacam software include pachymetry at 3 mm from the centre (Fig. 2) and the illustration of the averaged corneal thickness spatial profile as well as the percentage thickness increase from the centre to the periphery near the limbus, both of which are based on pachymetry readings from ring-averaged thickness along 22 imaginary circles that are centred on the thinnest point (Fig. 3, Oculus Pentacam Interpretation Guideline, 2nd ed)
[1]. An advantage of the Pentacam over similar systems is that it can provide non-central pachymetry data up to 5 mm away from the corneal centre, whereas earlier corneal imaging instruments, such as Orbscan, routinely provide data up to 4 and occasionally 4.5 mm away from the centre. Three versions of the Pentacam are currently in clinical use, the Pentacam Basic, Classic, and HR (high resolution). The basic and classic models differ mainly in their software features and the HR model also provides additional hardware updates [5]. While non-contact computerized pachymetry systems are advantageous in reducing inter-observer measurement variability, the complexity of the pachymetry information may present observers with challenges related to the question as to which data should be extracted and compared. For example, observers have the choice between points (Figs. 1 and 2) versus ring-averaged pachymetry (Fig. 3) and will also have to decide from which geographic location to obtain the measurements. The evaluation of peer-reviewed Pentacam studies that report on NCCT confirms that authors have indeed adopted a number of different strategies to extract and report non-central pachymetry measurements. This can be problematic as the use of different data extraction strategies could potentially obscure physiological variations such as changes in pupil size affecting the measurement [7]. Using ring-averaged pachymetry may lead to unexpected results in corneas of generally normal configuration and obscure regional variation in CT. The differences in data extraction and reporting not only make comparisons more difficult, but could potentially affect clinical decision-making, e.g. when assessing the effect of corneal crosslinking outside the corneal centre [2,3]. To date, there has been little discussion regarding different data extraction strategies. The most commonly used methods in previous studies are single-point and ring-averaged data extraction (see below). Some researchers have provided pachymetry for up to 22 0.4 mm increments from the centre [1], others have reported CT measured at a single distance in close proximity to the central cornea, e.g. 1.5 mm away from the centre [8]. The purpose of this paper is to review data extraction strategies used in different studies to report non-central corneal thickness measurements, with a focus on single-point and ring-averaged data obtained with the Pentacam system.
2. Materials and methods
Fig. 2. Numerical and colour-coded pachymetry map providing five data points, one central (apex) and four at nasal, temporal, superior, and inferior locations 3 mm away from the apex.
A literature search was carried out on 15 September 2013 using the United States National Library of Medicine PubMed database. Pre-defined search terms were used individually as well as in combination. The search terms included corneal thickness, peripheral corneal thickness, off-centre corneal thickness, non-central corneal thickness, pachymetry, Pentacam, and Scheimpflug imaging. The abstracts of studies with relevant titles were reviewed to ascertain relevance. All studies with relevant abstracts were retrieved and read in full. The option of ‘Related Publications’ was used to identify further studies. The reference lists of the articles were hand searched for additional relevant titles. Studies were included if non-central pachymetry obtained with the Pentacam system had been considered. From the included studies, data were extracted and entered into a data table (Table 1). Variables retrieved were country in which the study had been carried out, the number of eyes analysed, subject age, the type of central reference point, and the location of the most peripheral non-central corneal thickness reported in the study. NCCT values were obtained and also entered. For the purpose of succinctness, only the most ‘peripheral’, i.e. furthest away from the corneal centre measurement (along the horizontal meridian), was noted. This review focuses on the horizontal meridian, as vertical NCCT measurements are more likely
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
325
Fig. 3. Graphical and tabular illustration of the mean corneal thickness along concentric rings with the thinnest location as the central reference point. The upper graphic shows the progressive increase in absolute corneal thickness from the centre to the periphery (one data point per concentric ring). The lower graphic shows the percentage increase in corneal thickness. The respective ring-averaged pachymetry is given in the table below the graphs.
to be affected by shadows created by the eyelashes as well as the partial lid coverage of the cornea. 3. Results Seventeen relevant Pentacam studies published between 2005 and 2013 were identified. Combined, these studies assessed at least 3008 eyes of 2485 subjects, the age of subjects ranged from 7 to 83 years. The studies included individuals of various ethnic groups and were carried out in Australia [7,9,10], Austria [8], Brazil [1],
China [11–13], France [14], Germany [15,16], Iran [17], Malaysia [18], Mexico/USA [19], Spain [20], and the UK [4,21]. Non-central pachymetry measurements were obtained from corneal locations as close as 1.5 mm [8] to 5 mm away [4,21] from the corneal centre. Some studies included one eye per subject [11–13,16,18,21], whereas other studies analysed two eyes per subject [1,7,8,15,19]. A common data extraction strategy used in a number of studies was the use of ring-averaged NCCT [1,4,9,18,19,21], where pachymetry data along a concentric ring, usually centred on the thinnest location [1] are averaged and presented as a single pachymetry value
326
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
Table 1 Pentacam studies reporting non-central corneal thickness in normal subjects. Only the most peripheral data points reported in each paper are presented in this table. For studies that measured CCT at more than one location, only a single measurement is reported. First author
Year
Country
N
Mean age (years)
Central corneal thickness (mm ± SD)
Non-central corneal thickness (mean ± SD)
Location of most peripheral thickness measurement
Ruefer
2005
Germany
2006
Brazil
44 (range 18–83) Not given
534 ± 36 (A)
Ambrosio
364 eyes of 182 subjects 364 eyes of 196 subjects
609 ± 41 (N) 589 ± 40 (T) 712 ± 50
Buehl
2006
Austria
88 eyes of 44 subjects
24 (range 21–32)
535 ± 33 (ND)
3 mm from centre (right eyes) 8.8 mm ring diameter (4.4. mm radius) centred on thinnest point 1.5 mm from centre (presumably right and left eyes combined)
Lam
2007
China
2007
Germany
Shankar
2008
Australia
23 (range 20–26) 47 (range 18–77) 36 (range 7–65)
558 ± 33 (A)
Khoramnia
39 eyes of 39 subjects 76 eyes of 76 subjects 67 eyes of 35 subjects
Zheng
2008
China
926 eyes of 926 children 662 eyes of 662 adults
Children 12 (range 8–16) Adults 42 (range 30–68)
551 ± 33 (P) 536 ± 29 (P)
642 ± 37 (N) 613 ± 36 (T) 625 ± 35 (N) 606 ± 33 (T)
3 mm from pupil
Bourges Miranda
2009 2009
France UK
30 subjects 23 eyes of 23 subjects
37 27 (range 19–40)
Range 480–614 (ND) 546 ± 5 (SEM) (A)
Not given 803 ± 9 (SEM)
Prospero Ponce
2009
Mexico
597 ± 34
2010
Australia
39 (range 22–66) 27 (range 21–32)
516 ± 32 (ND)
Tyagi
163 eyes of 83 subjects 12 subjects
Within normative range of 475–596
Not given
3 mm from centre 10 mm ring diameter (5 mm radius) centred on thinnest location (first session) 6 mm ring diameter (3 mm radius from centre) 4–8 mm annular corneal region
Gonzales-Perez
2011
Spain
Not given
2012
UK
21 (range 20–29) 39 (range 19–76)
Not given
Fares
22 eyes of 22 subjects 67 eyes of 40 subjects
547 ± 35 (TH)
785 ± 48
Ahmadi Hosseini
2012
Malaysia
25
539 ± 35 (TH)
703 ± 38
Tyagi
2012
Australia
52 eyes of 52 subjects 14 eyes of 14 subjects
28 (range 20–33)
Not given
Ahmadi Hosseini
2013
Iran
No absolute data given, CCT measured over 0–4 mm annular corneal region 535 ± 79 (TH)
Huang
2013
China
50 eyes of 50 subjects 66 eyes of 66 subjects
25 35 (range 18–55)
537 ± 37 (TH)
540 ± 32 (A) 541 ± 37 (P)
539 ± 26 (A)
551 ± 35 (at 3 o’clocka ) 551 ± 34 (at 9 o’clocka ) 617 ± 36 (N) 600 ± 39 (T) 615 ± 34 (N) 599 ± 32 (T) 612 ± 42 612 ± 39
2.5 mm from apex (baseline, first session) 3 mm from centre 3 mm from pupil centre
3 mm radius, averaged from 8 meridians 10 mm ring diameter (5 mm radius from thinnest point) 8 mm ring diameter (4 mm radius from thinnest point) 4–8 mm annular corneal region
645 ± 32
5 mm from thinnest point
606 ± 28 (N) 585 ± 28 (T)
2.5 mm from apex (first reading)
A, apex; N, nasal; ND, central location not defined; P, pupil; T, temporal; TH, thinnest location. a The 3 o’clock position usually refers to the nasal aspect in right eyes, and the 9 o’clock position to the temporal aspect.
for this particular non-central location. Other authors chose to report measurements from individual corneal locations along various corneal meridians, e.g. nasal and temporal [7,11–13,15,16]. 3.1. Non-central pachymetry at 1–2 mm from the centre The terminology used to describe non-central locations varies across different studies. The term ‘peripheral’ has been used to describe pachymetry from as close as 1.5 and as far away as 5 mm from the corneal centre. Buehl and colleagues assessed ‘peripheral’ pachymetry in 88 eyes of 44 subjects aged between 21 and 32 years at a location 1.5 mm away from the corneal centre [8]. Even though these measurements have been described as being ‘peripheral’, it could be argued that the term refers to locations further away from the corneal centre, i.e. closer to the limbus. Unsurprisingly, the NCCT measurements obtained at the 1.5 mm locations were only slightly different from those at the centre (mean CCT 534 m versus PCT 551 m at nasal and temporal locations). Lam and Chen studied NCCT as part of a variability study [11]. The study included 39 eyes of 39 healthy Chinese subjects aged
20–26 years and corneal thickness was measured at 1.5 and 2.5 mm away from the corneal apex. Nasally, the mean NCCT at the 2.5 mm location was 617 m and temporally 600 m. Huang et al. examined central and mid-peripheral CT in a study that compared three rotating Scheimpflug topography systems including Pentacam [13]. Measurements were obtained from 66 eyes of 66 Chinese individuals aged 18–55 years. The NCCT measurements were obtained from locations up to 2.5 mm away from the apex. CCT, nasal, and temporal NCCT were 539 m, 606 m, and 585 m, respectively, indicating a 12% (nasal) and a 9% (temporal) increase in CT for the nasal and temporal locations as compared to the apex. Even though the maximum distance given in the methods-section is 2.5 mm from the apex, the results were labelled CT5mm , a notation that presumably refers to the ringaveraged notation also described in this review. Such notations may cause misunderstandings, as the reader may interpret this as measurements obtained at true 5 mm locations near the limbus. Measurements at 5 mm locations would likely be greater than those obtained at 2.5 mm and the percentage thickness difference would also be greater.
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
3.2. Non-central pachymetry at 3 mm from the centre Several research groups have assessed pachymetry at locations about 3 mm outside the corneal centre, for example in Germany [15,16], Australia [7], China [12], France [14], and Spain [20]. In one of the earliest Pentacam studies, Rüfer and colleagues assessed 364 eyes of 182 subjects aged 18–83 years at the ‘periphery’ 3 mm away from the corneal centre [15]. NCCT was 609 m (nasal) and 589 m (temporal) and therefore about 14% and 10% greater than the mean CCT of 534 m. Khoramnia et al. observed similar NCCT values of 615 and 599 m (nasal and temporal, respectively) in 76 eyes of 76 subjects aged 18–77 years [16]. The NCCT at those two locations was 14% and 11% thicker than CCT, respectively. In Australia, Shankar reported CCT and NCCT of 67 eyes of 35 healthy subjects aged 7–65 years as part of an instrument reliability study [7]. Three eyes were excluded due to the instrument providing a warning on the system’s ‘examination quality specification’. This warning flags up scans that could have been affected by loss of fixation, blinking, or poor instrument centration. The authors provide a valuable description of the Pentacam’s capacity to measure and report corneal thickness and highlight the instrument’s ability to provide CT from limbus to limbus. Shankar and co-authors also point out that the default NCCT location is set to 3 mm away from the pupil centre, but that NCCT is available for virtually all corneal locations by moving the cursor over the pachymetry map. The mean CCT was 541 m for both, pupil centre and corneal vertex CCT. Interestingly, the NCCT at 3 mm was identical for both nasal and temporal locations (612 m) when the pupil centre was used as the reference point. Using the corneal vertex as the central reference point provided a slightly different NCCT of 616 and 612 m for nasal and temporal aspects, respectively. Even though this difference is small, it illustrates that any nasal-temporal CT asymmetry could be dependent on the type of central reference point that is used. The authors note the effect of the pupil diameter variability and pupil decentration on NCCT during repeated measurements and recommend use of the corneal apex rather than the pupil centre as the central reference location for non-central pachymetry measurements by Pentacam. Zheng et al. studied NCCT 3 mm in a large population-based twin study [12]. The mean nasal NCCT was 625 and 642 m for adults and children, respectively. The mean corresponding temporal NCCT was considerably lower at 606 and 613 m for the two study group, respectively. Bourges and colleagues assessed the reliability of the Pentacam in comparison to a scanning slit topography system and ultrasound pachymetry and measured ‘peripheral’ CT of 30 healthy subjects with a mean age of 37 years 3 mm away from the corneal centre, using what was termed the ‘Oculus 3-D matrix files’ [14]. A special feature of this study was the generation of three-dimensional average pachymetry maps. These colour-coded pachymetry models allow for a more intuitive measurement comparison. The CCT ranged from 480 to 614 m, but is not clear whether these data were obtained with the Pentacam or one of the other instruments used in the study. While the inter-instrument differences are described in detail, absolute non-central pachymetry data were not provided. Prospero-Ponce et al. examined NCCT using ring-averaged data (6 mm diameter) as part of a comparative study of healthy individuals, keratoconus suspects, and post-LASIK patients [19]. NCCT was assessed in 163 eyes of 83 subjects (age 22–66 years), 103 of these eyes were healthy and had not undergone surgery. The ring-averaged NCCT was 597 m. Gonzales-Perez and colleagues assessed ‘peripheral’ corneal thickness up to 3 mm from the centre and along eight meridians as part of an instrument comparison study between Pentacam and
327
Orbscan II [20]. The study included 22 eyes of 22 healthy subjects aged 20–29 years. The authors describe the level of agreement between the two imaging systems, but absolute CT data were not included. 3.3. Non-central pachymetry beyond 3 mm from the centre Few studies have reported Pentacam pachymetry for locations beyond 3 mm from the centre [1,4,9,18,21]. In a study on the corneal spatial profile and volume distribution for the differentiation between normal and keratoconic eyes, Ambrosio and colleagues assessed 364 eyes of 196 normal patients in Brazil [1]. NCCT was determined for concentric 22 circles (0.4 mm steps apart) centred on the thinnest point. At the most peripheral location, on a circle of 8.8 mm diameter (corresponding radius 4.4 mm), the ring-averaged NCCT was 712 m, and the mean thinnest CT was 537 m. The percentage CT increases in from the thinnest location to the 8.8 mm circle averaged 33%. Tyagi and colleagues evaluated regional corneal thickness variations in 12 young subjects aged 21–32 to examine the effect of contact lens wear on corneal thickness [9]. In this study, NCCT was assessed at mid-peripheral (4 mm diameter) and peripheral (8 mm diameter) annular regions. Ahmadi-Hosseini et al. assessed 52 eyes of 52 patients in Malaysia in a study to describe the CT distribution and to discriminate between normal and ectatic corneas [18]. The mean ring-averaged peripheral thickness for locations of up to 8 mm diameter (4 mm radius from centre) averaged 703 m. With a percentage thickness increase of 29%. The most peripheral CT measurement provided on the numerical pachymetry maps available from the Pentacam system is for locations close to the limbus 5 mm away from the corneal centre. Fares and colleagues assessed NCCT using two different strategies, namely (i) single point pachymetry measurements at 3 and 7 mm from the apex (radius 1.5 and 3.5, respectively) and (ii) ringaveraged measurements for locations up to 10 mm (5 mm radius) where the concentric circles were centred on the thinnest location [4]. The principal aim of the study was to assess the correlation between central and peripheral CT and to examine whether central pachymetry measurements could be considered sufficient on their own, i.e. without consideration of NCCT. The ring-averaged NCCT at the most peripheral location was 785 m, which corresponds to a 43% increase. As part of a Pentacam repeatability study, Miranda and colleagues assessed 23 eyes of 23 subjects with a mean age of 27 years [21]. Peripheral ring-averaged pachymetry of up to 10 mm diameter centred on the thinnest location was obtained and averaged 803 m for this most peripheral location. In their study the authors point out that the increased variability of peripheral CT measurements may be associated with regional corneal asymmetries in CT, which could be interpreted as an argument for the reporting of point- rather than ring-averaged pachymetry. In a study that aimed to examine corneal swelling in response to rigid contact lens wear, Tyagi and coworkers used data from an annular region 4–8 mm away from the corneal centre [10]. Very recently, Ahmadi Hosseini and colleagues reported NCCT for locations up to 5 mm away from the thinnest point with a mean of 645 ± 32 m [17]. These data were obtained from a normal cohort and NCCT at 5 mm was substantially lower than that of a 4 mm location reported in an earlier study by the same lead author (703 ± 38 m), even though they were obtained further away from the centre [18]. 4. Discussion This review discusses approaches that have been adopted for the reporting of non-central pachymetry obtained with the
328
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
Fig. 4. Illustration of two successive Pentacam scans. The data represent mid-peripheral corneal thickness (3 mm) at the four main meridians (superior, nasal, inferior, and temporal) as reported by Shankar et al. [7]. Reporting point-pachymetry from various meridians indicates differences in the measurements. Averaging the four mid-peripheral values for each scan would provide similar mean thickness values, thereby obscuring any existing differences.
Pentacam system. A main difference between studies was the use of either point-pachymetry from a defined location and ring-averaged pachymetry.
mean CT of 823 m nasally and 772 m temporally was observed. Ring-averaging measurements would obscure deviations from the normal corneal configuration, of which the nasal-temporal NCCT asymmetry is frequently a typical characteristic.
4.1. Clinical relevance of peripheral pachymetry Pachymetry measurements outside of the corneal centre have been used in a number of studies investigating abnormal corneal structure as well as in pre- and postoperative assessments of surgical interventions and have been shown to provide valuable clinical information. Pentacam pachymetry maps have been used for the differentiation of normal thin from ectatic corneas [1]. Central and non-central pachymetry can be used to differentiate between mild to moderate keratoconus and candidates suitable for photorefractive keratectomy [17], to determine corneas outside the normal corneal thickness range, for example in assessments of contact lens-related changes [10]. Relative peripheral pachymetry can be useful in the clinical classification of Fuchs’ endothelial dystrophy [22]. Peripheral Pentacam pachymetry has been utilized in preand postoperative assessments of deep anterior lamellar keratoplasty [23], to evaluate the peripheral edges of the donor button in Descemet’s Stripping Automated Endothelial Keratoplasty, as well as in the subsequent monitoring of postoperative progressive peripheral graft thinning [24]. The Pentacam instrument provides posterior corneal elevation analysis and such assessments have been used to evaluate the mid-peripheral and peripheral cornea after laser refractive surgery for myopia and myopic astigmatism [25]. Peripheral assessments have also been made in the management of post-LASIK ectasia [26]. A number of studies have reported NCCT using ring-averaged data [1,4,9,18,19,21]. This approach provides a single pachymetry reading for points on a circle at a given distance from a central reference point (covering various radial meridians). The advantage of this modality is the use of just a single figure, which is easy to interpret. A disadvantage of reporting ring-averaged pachymetry is that it does not reflect regional intracorneal asymmetries. A recent study carried out at Glasgow Caledonian University in collaboration with the University of Valladolid confirmed a substantial nasal-temporal asymmetry in CT [27]. The magnitude of this asymmetry increased progressively from to the centre towards the limbus, with nasal readings being consistently greater than the corresponding temporal readings. At the most peripheral location (5 mm from centre), a
4.2. Examples of the impact of ring-averaging data on the interpretation of pachymetry Regional structural differences of the cornea have been shown to influence the effect of corneal crosslinking [3], in that crosslinking will be relatively less effective at corneal locations of greater thickness than compared to those of lower thickness (i.e. corneal crosslinking may be relatively less effective nasally than temporally). The treatment effect of corneal crosslinking is reduced by about a third to approximately 65% at 3 mm away from the centre [3]. Interpolation of the treatment results to other corneal locations needs to take into account regional asymmetries, as the nasal peripheral cornea is usually thicker than the temporal periphery [28]. However, these regional asymmetries are obscured if, for example, ring-averaged data were reported, making estimates of effectiveness of treatment more difficult [18,19,21]. A second example of the disadvantage of using ring-averaged data is related to potential problems associated with increased CT variability due to changes in pupil size [7]. The magnitude of these effects may be substantial enough to warrant clinical significance. The sketches in Fig. 4 illustrate two consecutive Pentacam scans and the data shown are as presented in a paper by Shankar and colleagues [7], representing central and mid-peripheral (3 mm) pachymetry. The data are presented as point data for each of the four principal meridians. If one were to use the ring-averaging approach, by which the four mid-peripheral readings are averaged to obtain a single reading for the 3 mm location, the mean mid-peripheral corneal thickness would average 613 m for scan 1 (Fig. 4A) and 611 m for scan 2 (Fig. 4B), thereby indicating no substantial difference between the two images if only ring-averaged date were considered. Analysis of each individual meridian, however, reveals that the change in pupil size in this example has led to a different pachymetry reading with an underestimation of corneal thickness of −28 m temporally and an overestimation of +28 m nasally. These differences would have been obscured if ring-averaged pachymetry had been applied. The reporting of data from the principal meridians, e.g. nasal, temporal, superior,
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
and inferior provides an opportunity to identify changes in pupil diameter more easily. A third example where using ring-averaged data could lead to uncertainty is the comparison of two Pentacam studies. In these studies, pachymetry was obtained from two samples of participants, one in Malaysia and one in Iran. These two studies included a similar number of subjects of similar average age and with similar CCT. One study used ring-averaged data from 5 mm locations (mean ± SD 645 ± 32 m) [17], which were on average considerably lower than the pachymetry values for 4 mm locations in the second study (703 ± 38 m) [18]. NCCT in the study using the more peripheral 5 mm location was considerably lower than the data reported for a 4 mm location. While CT at 5 mm could be expected to be greater than 4 mm from the central reference point, the 4 mm pachymetry data were on average 63 m or approximately 10% greater than the 5 mm data. A possible reason for this discrepancy could be that the two samples display considerable inherent differences, e.g. due to their ethnic background. However, the reason for the finding cannot be ascertained without the knowledge of meridional data. 4.3. Further issues related to non-central pachymetry Previous studies show that the term ‘peripheral’ can be used in several ways. The term ‘peripheral’ has been used to describe corneal thickness measurements outside the corneal centre and has been applied to corneal locations as close as 1.5 mm [8] as well as up to 5 mm from the corneal centre [4]. Not all of these locations can truly be considered to be ‘peripheral’. Non-central pachymetry data from just 1.5 mm outside the centre are likely to differ substantially from readings that were obtained 5 mm away from the centre. Using a more differentiated terminology may be beneficial, i.e. the term ‘peripheral’ could perhaps be restricted to measurements obtained at least 4 mm away from the corneal centre. Measurements obtained between 1.5 and 3.5 mm could be classed as ‘mid-peripheral’ or ‘para-central’, as has been used in a previous study [20]. Any measurements within the central 3 mm (1.5 mm radius) could be classed as ‘central’. Given that corneal thickness increases progressively and asymmetrically from the centre to the limbus, it could be beneficial to agree on more clearly defined terminology for corneal locations. In addition to NCCT, the Pentacam system provides up to three central pachymetric reference points, namely (i) pupil centre, (ii) apex, and (iii) thinnest point pachymetry. The pupil centre is defined as the geometrical centre point of pupil. According to the information provided in the Pentacam instruction manual (version G/70700/1105/e), the apex can be interpreted as the central location at which there is no deviation on either the x- or the y-axis of the anterior surface. The thinnest point is a location that is commonly found slightly off-centre in the inferior-temporal quadrant, but thinnest point pachymetry does not differ significantly from corneal apex thickness [4]. The age range in the studies included in this review varied considerably. As peripheral corneal thickness is inversely associated with age [22,28], interpretation of NCCT should ideally consider the relative age-dependent decline. This is likely to be of greater importance when considering pachymetry readings that are obtained from locations close to the limbus, where the age-related effect is most pronounced. The most advanced Pentacam model, the Pentacam HR provides the user with a number of additional features such as an improved optical design, a 1.45-megapixel camera, and enhanced fixation options [5,29]. With the HR model it is possible to obtain five times the number of data points as compared to the standard Pentacam. While more data points do not necessarily lead to a higher reliability of measurements, the HR model has been
329
reported to provide improved precision of CCT measurements. Corneal apex pachymetry showed the best repeatability (reported as within subject standard deviation) when the cornea fine scan was used (3.15 m), and only marginally poorer repeatability when the 25 pictures scan was used (3.74 m). Peripheral pachymetric repeatability assessed at 4 mm inferiorly was best with the fine scan (7.86 m), and similar when the 25 (8.69 m) or the 50 picture scan (8.24 m) were used. In this reliability study, the authors suggest that the good repeatability of the Pentacam HR could be associated with improvements of the instrument over the standard Pentacam [29]. A previous study that evaluated the reliability of the standard Pentacam showed that the repeatability of pachymetry at the corneal apex was good (−1.04 ± 7.17 m, mean difference ± SD). The study also highlighted a potential problem, namely that the pupil centre is variable and that this variability has an effect on peripheral pachymetry measurements, as repeated peripheral measurement points do not correspond, due to differences in the location of the pupil centre. This effect can be overcome by using the corneal apex as the central reference point, which provided satisfactory peripheral reliability (9.01 ± 8.34 m, mean difference ± SD at three millimetres inferiorly from the corneal apex) [7]. From these studies it can be concluded that, based on the standard deviation between repeated measurements, the Pentacam and the Pentacam HR models provide a comparable reliability of central and peripheral pachymetry measurements. A recent study has investigated the advantage of measuring NCCT by examining the relationship between central and noncentral CT to determine if reliance on central measurements should suffice [4]. The reasoning was that if central and peripheral CT were closely related, this could perhaps eliminate the need to obtain NCCT readings. The study showed a statistically significant correlation between central and non-central CT at locations of up to 5 mm away from the centre (r ≥ 0.635; p < 0.001). Even though approximately 47% of corneal thickness at the 7 mm location could be predicted by CCT, more than 50% of the variability could not be predicted. It was concluded that for most purposes CCT can guide the prediction of NCCT. With contemporary corneal imaging becoming more widely available and NCCT measurements being of potential additional benefit in surgical procedures affecting the mid-peripheral and peripheral corneal zones, e.g. intracorneal ring insertion and limbal relaxing incisions, it could be argued that NCCT should not be neglected. This review seeks to illustrate commonly used approaches to report Pentacam pachymetry. It is hoped that this paper will stimulate and contribute to a discussion as to which strategy is likely to be the most effective for the reporting of non-central pachymetry. This review does not aim to disconsider in any way the methods mentioned in this article, but simply intends to highlight some of the benefits and disadvantages of methods currently used to report Pentacam pachymetry. Further studies would be useful to confirm the clinical importance of the regional differences and asymmetries in corneal thickness. If such regional differences are considered important (indicated by the increasing number of studies reporting such data) then ring-averaged data should be used cautiously. 4.4. How can a more reliable comparison of pachymetry be achieved? Thinnest point data and the measures resulting from concentric ring centred on the thinnest location may be the most appropriate in the detection and classification of keratoconus. However, the assessment of regional variations in corneal thickness could be enhanced by reporting data from at least four meridians. The horizontal meridian is least likely to be affected by partial lid coverage.
330
S. Jonuscheit / Contact Lens & Anterior Eye 37 (2014) 323–330
Alternatively, the presentation of a pachymetry map may be even more informative. It is acknowledged that map interpretation requires more time, which may limit its utility in a busy clinic environment. From the examples provided above it can be concluded that point-pachymetry would allow for detection of any substantial regional asymmetries while being easy to obtain and interpret. Regional variations in CT between samples as well as possible effects of physiological changes such as pupil size are easily recognizable. In conclusion, the Pentacam system provides a range of options for the reporting of CT data. Pachymetry measurements can be obtained from locations up to 5 mm away from the corneal centre. As has been illustrated above, different strategies have been used in peer-reviewed articles to report non-central pachymetry data. For some clinical applications, ring-averaged pachymetry may be sufficient. For detailed assessments of regional asymmetries such as the nasal-temporal asymmetry the consideration of single-point pachymetry data along the principal meridians may allow for a more reliable assessment. Funding This work was supported by Santander Universities Fund UK. Conflict of interest The author declares no conflict of interest. Acknowledgements The author would like to thank the reviewers for their constructive comments and support in improving the manuscript. The author also thanks Peter Rafferty, Graeme Kennedy, Andreas Steinmueller, and Sven Reisdorf for helpful discussions on optical aspects of the Pentacam. References [1] Ambrósio Jr R, Alonso RS, Luz A, Coca Velarde LG. Corneal-thickness spatial profile and corneal-volume distribution: tomographic indices to detect keratoconus. J Cataract Refract Surg 2006;32:1851–9. [2] Rehnman JB, Janbaz CC, Behndig A, Lindén C. Spatial distribution of corneal light scattering after corneal collagen crosslinking. J Cataract Refract Surg 2011;37:1939–44. [3] Koller T, Schumacher S, Fankhauser F, Seiler T. Riboflavin/ultraviolet a crosslinking of the paracentral cornea. Cornea 2013;32:165–8. [4] Fares U, Otri AM, Al-Aqaba MA, Dua HS. Correlation of central and peripheral corneal thickness in healthy corneas. Cont Lens Anterior Eye 2012;35: 39–45. [5] Oliveira CM, Ribeiro C, Franco S. Corneal imaging with slit-scanning and Scheimpflug imaging techniques. Clin Exp Optom 2011;94:33–42. [6] Villavicencio O, Belin MW, Ambrósio R, Steinmueller A. Corneal pachymetry: new ways to look at an old measurement. J Cataract Refract Surg 2014;40:695–701.
[7] Shankar H, Taranath D, Santhirathelagan CT, Pesudovs K. Anterior segment biometry with the Pentacam: comprehensive assessment of repeatability of automated measurements. J Cataract Refract Surg 2008;34:103–13. [8] Buehl W, Stojanac D, Sacu S, Drexler W, Findl O. Comparison of three methods of measuring corneal thickness and anterior chamber depth. Am J Ophthalmol 2006;141:7–12. [9] Tyagi G, Collins M, Read S, Davis B. Regional changes in corneal thickness and shape with soft contact lenses. Optom Vis Sci 2010;87:567–75. [10] Tyagi G, Collins MJ, Read SA, Davis BA. Corneal changes following short-term rigid contact lens wear. Cont Lens Anterior Eye 2012;35:129–36. [11] Lam AKC, Chen D. Pentacam pachometry: comparison with non-contact specular microscopy on the central cornea and inter-session repeatability on the peripheral cornea. Clin Exp Optom 2007;90:108–14. [12] Zheng Y, Huang G, Huang W, He M. Distribution of central and peripheral corneal thickness in Chinese children and adults: the Guangzhou twin eye study. Cornea 2008;27:776–81. [13] Huang J, Ding X, Savini G, Pan C, Feng Y, Cheng D, et al. A comparison between Scheimpflug imaging and optical coherence tomography in measuring corneal thickness. Ophthalmology 2013;120:1951–8. [14] Bourges JL, Alfonsi N, Laliberté JF, Chagnon M, Renard G, Legeais JM, et al. Average 3-dimensional models for the comparison of Orbscan II and Pentacam pachymetry maps in normal corneas. Ophthalmology 2009;116:2064–71. [15] Rüfer F, Schröder A, Arvani M-K, Erb C. Central and peripheral corneal pachymetry – standard evaluation with the Pentacam system. Klin Monatsbl Augenheilkd 2005;222:117–22. [16] Khoramnia R, Rabsilber TM, Auffarth GU. Central and peripheral pachymetry measurements according to age using the Pentacam rotating Scheimpflug camera. J Cataract Refract Surg 2007;33:830–6. [17] Ahmadi Hosseini SM, Abolbashari F, Niyazmand H, Sedaghat MR. Efficacy of corneal tomography parameters and biomechanical characteristic in keratoconus detection. Cont Lens Anterior Eye 2013;37:26–30. [18] Ahmadi Hosseini SM, Mohidin N, Abolbashari F, Mohd-Ali B, Santhirathelagan CT. Corneal thickness and volume in subclinical and clinical keratoconus. Int Ophthalmol 2012;33:139–45. [19] Prospero Ponce CM, Rocha KM, Smith SD, Krueger RR. Central and peripheral corneal thickness measured with optical coherence tomography, Scheimpflug imaging, and ultrasound pachymetry in normal, keratoconus-suspect, and post-laser in situ keratomileusis eyes. J Cataract Refract Surg 2009;35:1055–62. [20] González-Pérez J, Gonzalez-Meijome JM, Rodríguez Ares MT, Parafita MA. Topographic paracentral corneal thickness with Pentacam and Orbscan: effect of acoustic factor. Eye Contact Lens 2011;37:348–53. [21] Miranda MA, Radhakrishnan H, O’Donnell C. Repeatability of corneal thickness measured using an Oculus Pentacam. Optom Vis Sci 2009;86:266–72. [22] Repp DJ, Hodge DO, Baratz KH, McLaren JW, Patel SV. Fuchs’ endothelial corneal dystrophy. Ophthalmology 2013;120:687–94. [23] Riss S, Heindl LM, Bachmann BO, Kruse FE, Cursiefen C. Pentacam-based big bubble deep anterior lamellar keratoplasty in patients with keratoconus. Cornea 2012;31:627–32. [24] Scorcia V, Matteoni S, Scorcia GB, Scorcia G, Busin M. Pentacam assessment of posterior lamellar grafts to explain hyperopization after Descemet’s stripping automated endothelial keratoplasty. Ophthalmology 2009;116:1651–5. [25] Zhang L, Wang Y. The shape of posterior corneal surface in normal, post-LASIK, and post-epi-LASIK eyes. Invest Ophthalmol Vis Sci 2010;51:3468–75. [26] Kanellopoulos AJ, Binder PS. Management of corneal ectasia after LASIK with combined, same-day, topography-guided partial transepithelial PRK and collagen cross-linking: the Athens protocol. J Refract Surg 2010;27:323–31. [27] Jonuscheit S, Doughty MJ, Martin R, Rio San Cristobal A, Mackintosh L, MacTaggart D, et al. Body mass index, peripheral corneal thickness and anterior chamber depth in young European adults – a pilot study. ARVO Meet Abstr 2013;54:524. [28] Jonuscheit S, Doughty MJ. Evidence for a relative thinning of the peripheral cornea with age in white European subjects. Invest Ophthalmol Vis Sci 2009;50:4121–8. [29] McAlinden C, Khadka J, Pesudovs K. A comprehensive evaluation of the precision (repeatability and reproducibility) of the Oculus Pentacam HR. Invest Ophthalmol Vis Sci 2011;52:7731–7.
