Comparison of normal and keratoconic corneas by Galilei Dual-Scheimpflug Analyzer

ARTICLE IN PRESS

G Model CLAE-624; No. of Pages 7

Contact Lens & Anterior Eye xxx (2013) xxx–xxx

Contents lists available at SciVerse ScienceDirect

Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae

Comparison of normal and keratoconic corneas by Galilei Dual-Scheimpflug Analyzer Selim Demir a,∗ , Barıs¸ Sönmez b , Volkan Yeter c , Hüseyin Ortak a a b c

Departments of Ophthalmology, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey Departments of Ophthalmology, Memorial Hospital, Istanbul, Turkey Department of Ophthalmology, Erzincan University Mengücek Gazi Education and Research Hospital, Erzincan, Turkey

a r t i c l e

i n f o

Article history: Received 13 September 2012 Received in revised form 30 March 2013 Accepted 2 April 2013 Keywords: Keratoconus Anterior segment imaging Scheimpflug Galilei Clinical examination

a b s t r a c t Background and objective: To determine the efficacy of different Galilei Scheimpflug-Analyzer (GSA) parameters in discriminating between keratoconic and myopic eyes. Patients and methods: GSA measurements were obtained for 67 patients (67 eyes) with keratoconus and 151 patients (151 eyes) with myopia or myopic astigmatism. Several parameters, provided by the software or derived from the elevation maps, were evaluated and compared for the two groups. Results: Between the two groups, statistically significant differences were observed for all corneal parameters obtained by GSA (P < 0.001) except for the anterior chamber depth (P = 0.149). ROC analysis determined that posterior corneal elevation was the best predictive parameter (area under the curve: 0.99). The posterior corneal elevation, at a cut-off value of 18.5 ␮m, had 98.5% sensitivity and 98.3% specificity in discriminating keratoconus from myopic eyes. Conclusion: Elevation, pachymetric and keratometric parameters measured by the GSA, as well as the specific predictive GSA software parameters can effectively distinguish advanced keratoconus from myopic corneas. Also, keratoconus that is easily diagnosed by other means can be diagnosed easily by GSA software parameters. © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

1. Introduction Keratoconus is a noninflammatory ectatic disorder of the cornea characterized by corneal thinning and ectasia of the cornea that causes irregular astigmatism and deterioration of vision [1]. The most common methods used for diagnosis of keratoconus are Placido disk-based corneal topography and central pachymetry [2–3]. Placido disk-based topography evaluates only the anterior surface of the cornea without any posterior surface details [4]. Ultrasound pachymetry is a contact device, and correct alignment and centralization of the corneal probe over the cornea is necessary for obtaining precise measurement of the central corneal thickness [5]. Recent developments in anterior segment imaging methods provide more detailed, three-dimensional information about the structure of the cornea [6–8]. Anterior segment imaging devices with different operating principles are used today. Operating using the principles of the Scheimpflug method are the Pentacam and Galilei devices. The

∗ Corresponding author at: Gaziosmanpas¸a Üniversitesi Tıp Fakültesi Hastanesi, Göz Hastalıkları Anabilim Dalı, Tokat, Turkey. Tel.: +90 507 331 39 89; fax: +90 356 252 16 25. E-mail address: [email protected] (S. Demir).

Galilei has recently entered clinical use with high sensitivity [9–11]. In the literature, many studies have been reported that discriminate between normal and keratoconic eyes with the Pentacam [6–8,12–14], but this study is the first performed with the Galilei. The Galilei Dual-Scheimpflug Analyzer (GSA) (Ziemer Ophthalmic Systems AG, Port, Switzerland) is also a Scheimpflug imaging system. Unlike the Pentacam (Oculus Optikgerate GmbH, Wetzlar, Germany), the Galilei system includes two rotating cameras (as opposed to Pentacam’s one) and Placido disk topography technology. The two rotating cameras provide images from both sides of the slit during corneal scanning, and thus, minimize the effect of decentralization, due to eye movements, on corneal pachymetry and posterior corneal curvature measurements. While the single-Scheimpflug method evaluates corneal thickness and height, it approximates corrections from the surface slope. Integration of Placido disk topography technology (20 monochrome ring, 200 mm diameter) in the GSA also provides more accurate topographic data [15–17]. Thus, more accurate anterior corneal curvature measurements could be obtained. The main purpose of this study, therefore, was to identify those parameters obtained from dual-Scheimpflug imaging that are most useful in distinguishing morphological features from normal and keratoconic corneas.

1367-0484/$ – see front matter © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clae.2013.04.001

Please cite this article in press as: Demir S, et al. Comparison of normal and keratoconic corneas by Galilei Dual-Scheimpflug Analyzer. Contact Lens Anterior Eye (2013), http://dx.doi.org/10.1016/j.clae.2013.04.001

G Model CLAE-624; No. of Pages 7

ARTICLE IN PRESS S. Demir et al. / Contact Lens & Anterior Eye xxx (2013) xxx–xxx

2

2. Patients and methods The medical records of 67 consecutive keratoconic patients and 151 consecutive myopic individuals, who were candidates for refractive surgery, at the Ophthalmology Department of Ondokuz Mayıs University Hospital, Samsun, between January 2007 and December 2008 were reviewed. The data from the GSA of all individuals was evaluated for this study. The mean ages of the keratoconus and control groups were 25.7 ± 6.7 and 26.3 ± 8.3, respectively. A cornea was considered keratoconic if it had (1) an irregular cornea determined by both distorted keratometric mires and distortion of retinoscopic red reflex (scissoring reflex) and (2) at least one of the following clinical signs: subepithelial iron accumulation at the base of the cone (Fleischer ring), Descemet’s membrane striae, or subepithelial fibrosis consistent with keratoconus. Patients with serious corneal scarring, a history of previous ocular surgery, or any other ocular pathology were excluded. The data for the mean keratometry (K) was obtained from the topographic map of the GSA. Patients were grouped according to the Amsler-Krumeich keratoconus classification using mean keratometric and central corneal thickness values from the Galilei Scheimpflug photographic camera system [18]. The control group consisted of consecutive myopic patients who were candidates for refractive surgery. The patients in the 85 control group had refractive errors of between −1.00 D and −8.00 86 D sphere and at most 3.0 D cylinder without other ocular pathologies. These patients were carefully evaluated for keratoconus using topographical analysis (KR-9000pw, Topcon, Tokyo, Japan), and the patients with suspected keratoconus were not included in the control group. The anterior segment measurements were obtained with the Galilei Dual-Scheimpflug Analyzer (Ziemer Ophthalmic Systems AG, Port, Switzerland). The patient was seated with his chin on the chin rest and forehead against the forehead strap and asked to fixate forward on a target. A real-time image of the patient’s eye was generated on the computer screen, aligned on the visual axis represented by the center of the four white spots, and the corneal apex was marked. The operator manually focused and aligned the image. The device’s indicators must be manually aligned with the appropriate alignment of the instrument on the horizontal, vertical, and antero-posterior axes. After scanning, the quality of the scan is checked by the device software for four quality parameters on the verify screen of the device. These parameters are ‘Motion Compensation’, ‘Placido’, ‘Scheimpflug’, and ‘Motion Distance’. ‘Motion Compensation’ is an important factor that should be higher than 85%. It indicates how well the patented eye tracker system was able to follow the eye movement during the procedure. Eye tracking is critical for combining all the data points of the different images that are taken in one measurement. ‘Motion Distance’ may be of less importance and can be as low as 70%. ‘Placido’ and ‘Scheimpflug’ are also important properties of a scan. The minimum quality percentages of the ‘Placido’ and ‘Scheimpflug’ parameters should be 85% and 90%, respectively. Finally an ‘Overall Quality’ is calculated by the software of the device for general information purposes only and has no minimum required percentage associated with it. For these parameters, software indicates a reliability sign as ‘OK’ near the names of these, and then the operator can accept the scan as reliable. Measurements which the device software marked as ‘reliable’ were included in the study, while unreliable scans were repeated until reliable values were obtained. For both groups, single eye measurements of individuals were taken. If both eyes were fit for measurement, the right eye was preferred. If right eye measurements could not be carried out due to corneal scarring or unilateral surgical history for the

keratoconic group, left eye measurement was taken. Right eye measurements were included in the study for all control group individuals. Central and Thinnest Corneal Thicknesses (CCT and TCT): The thickness of the cornea’s central portion and thinnest point. Anterior and Posterior Corneal Elevations (ACE and PCE): Like the Pentacam, the Galilei produces elevation data for the anterior and posterior corneal surfaces. The Galilei then displays the data in a two dimensional color-coded map. Shades of green represent points close to the reference surface, or the best fit sphere (BFS), with warmer and cooler shades representing points above and below the BFS, respectively. The highest values of the ACE and PCE in a 9 mm diameter of the area of the central cornea were used for the control and keratoconic groups. SimKavg and Kavg: The SimKavg and Kavg are half of the summation of the steep and flat axes. For example: SimKavg = (SimKf + SimKs)/2. In order to obtain a corneal power of 45 D at a radius of 7.5 mm, the keratometric index has been adjusted to 1.3375. SimK parameters are calculated with the so-called keratometric index, which is known from Placido topographers, and is equal to 1.3375. This does not correspond to the actual index of refraction of the cornea (1.376) since it takes into account the posterior surface parameters calculated with a keratometric index and called simulated (SimKf, SimKs). SimK steep (SimKs) and SimK flat (SimKf) are calculated from the two perpendicular meridians with the greatest difference in corneal power, from a 0.5 mm to 2.0 mm radius on the anterior surface. Mean Total Corneal Power (MK): This is the average dioptric power of the total cornea (anterior and posterior) over a radius of 0.5–2.0 mm. Anterior Chamber Depth (ACD): The ACD is the distance between the endothelium and the anterior lens at the center of cornea. The direction of this distance measurement is normal to the lens surface. The ACD is the average of all measured Scheimpflug scans.

2.1. The specific parameters (indices) included in Galilei software for the prediction of keratoconus Inferior–superior index (I–S): The I–S is the subtraction of the superior from the inferior average dioptric power within the 3 mm peripheral cornea area. Surface asymmetry index (SAI): The SAI is the centrally-weighted average of differences in corneal power. Centrally-weighted values are obtained by dividing the surface area of each corneal ring into the average power for each ring. The SAI parameter is then determined by dividing the summation of these weighted values by the total summation of the reciprocals of the ring areas. Surface regularity index (SRI): The SRI shows the degree of regularity (spherical property) of a surface. This index sums the meridional mire-to-mire power changed over the apparent entrance pupil, increasing as topographic irregularities increase. SRI is the central weighted and calculated data from the inner 10 rings. If the SRI value of a surface is zero, the spherical surface is perfectly smooth. Irregular astigmatism index (IAI): The IAI is the summation of area-corrected dioptric variations normalized by the average corneal power and number of all measured points. It is measured as the average summation of inter-ring power variations along every semimeridian for the entire analyzed corneal surface. Differential sector index (DSI): The DSI is the greatest difference in average area-corrected power among any two 45◦ corneal sectors. Opposite sector index (OSI): The OSI index shows the greatest difference in average area-corrected power among opposite 45◦ sectorial corneal areas.

Please cite this article in press as: Demir S, et al. Comparison of normal and keratoconic corneas by Galilei Dual-Scheimpflug Analyzer. Contact Lens Anterior Eye (2013), http://dx.doi.org/10.1016/j.clae.2013.04.001

G Model CLAE-624; No. of Pages 7

ARTICLE IN PRESS S. Demir et al. / Contact Lens & Anterior Eye xxx (2013) xxx–xxx

3

Table 1 Anterior segment parameters and comparisons between groups. Parameters

Keratoconus (mean ± SD)

ACE (␮m) PCE (␮m) ACD (mm) SimKavg (D) Kavg (D) MK (D) TCT (␮m) CCT (␮m) I–S SAI SRI IAI DSI OSI CSI ACP

29.5 57.7 3.30 51.5 −7.8 50.8 459.8 492.3 11.11 7.39 2.35 2.31 14.26 10.01 3.96 52.38

± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±

14.9 (5–96) 25.8 (20–190) 0.29 (2.55–3.80) 4.7 (43.3–65.2) 0.8 (−9.9 to −6.3) 4.9 (42.9–66.6) 43.8 (308–491) 37.0 (414–566) 8.68 (0.19–48.53) 5.66 (1.35–36.54) 0.99 (0.91–4.55) 3.12 (0.17–18.91) 11.44 (2.24–38.05) 6.96 (0.82–35.46) 2.88 (−2.85 to 14.65) 4.96 (43.45–65.51)

Control (mean ± SD) 2.5 5.25 3.31 43.28 −6.1 43.1 545.8 556.4 0.78 0.54 0.82 0.49 1.75 0.78 0.22 43.60

± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±

P-value

2.7 (0–8) 4.8 (0–25) 0.30 (2.37–4.08) 1.72 (40.16–47.59) 0.2 (−7.2 to −5.5) 1.6 (40.1–47.0) 36.5 (425–616) 34.7 (437–632) 0.56 (0.01–2.90) 0.33 (0.16–1.30) 0.45 (0.05–1.50) 0.19 (0.06–0.88) 1.13 (0.43–4.45) 0.80 (0.03–3.09) 0.42 (−0.77 to 0.81) 1.48 (40.37–47.70)

<0.001 <0.001 0.149 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

ACD, anterior chamber depth; ACE, anterior corneal elevation; CCT, central corneal thickness; SD, standard deviation; Kavg, average posterior corneal keratometry; MK, mean keratometric value; PCE, posterior corneal elevation; SimKavg, average anterior corneal keratometry; TCT, thinnest corneal thickness; I–S, difference between the inferior and superior corneal thicknesses in the central 3 mm area; SAI, surface asymmetry index; SRI, degree of regularity (spherical property) of corneal surface; IAI, irregular astigmatism index; DSI, differential sector index, the difference between the two 45◦ sectors with the highest mean keratometric difference; OSI, opposite sector index, the difference between the two opposite 45◦ sectors with the highest difference; CSI, center/surround index, the mean keratometric difference between the central 3 mm area and the 3–6 mm corneal ring; ACP, Average corneal power.

Center/surround index (CSI): The CSI is the average areacorrected power difference between the central area (3 mm diameter) and residual area (3–6 mm). Average central dioptric power (ACP): The ACP is the average dioptric power within the central 3 mm area. 2.2. Statistical analyses After coding the data obtained during the investigation, it was analyzed using SPSS 15.0. Normality tests were applied to all measurement variables. Normally distributed continuous variables were defined by mean ± standard deviation, while frequency data was defined as percentages (%). For the normally distributed measurement variables, t-tests were used to compare the groups. The Pearson correlation test was used to compare the correlation. For non-normally distributed variables, the Mann–Whitney U test was used and the correlation was tested using the Spearman Correlation Test. The receiver operating characteristic (ROC) values were compared for all parameters between the two groups. ROC analysis was used for specificity and sensitivity assessment. All the evaluations were completed using SPSS 15.0. A statistical significance level of P < 0.05 was accepted for all tests. 3. Results The mean age of the 67 patients with keratoconus (40 male, 27 female) was 25.7 ± 6.7 years (10–52), while the 151 control group individuals (84 male, 67 female) had a mean age of 26.3 ± 8.3 years (15–54). There was no statistically significant difference between the two groups in terms of age or sex (P = 0.784 and P = 0.493, respectively). In control group, 151 right eyes were included for the study. In keratoconic group, 38 right eyes and 29 left eyes were included for the study. There were 14 eyes with stage I (mean K value ≤48.00 D), 28 eyes with stage II (mean K value between 48.00 D and 53.00 D), 15 eyes with stage III (mean K value between 53.00 D and 55.00 D), and 10 eyes with stage IV (mean K value >55.00 D) keratoconus. The spherical refraction value was −3.98 ± 3.85 for the keratoconus patients and −3.53 ± 2.45 for the control group. The difference between groups was not statistically significant (P = 0.958). The cylindrical refraction value was −3.97 ± 2.15 for the keratoconus patients and −1.12 ± 1.44 for the control group,

a statistically significant difference (P < 0.001). In Table 1, the comparison of the anterior segment parameters obtained by the GSA is shown. All the evaluated values in this table, except for the anterior chamber depth (P = 0.149), were statistically different for the two groups (P < 0.001). The relationship between the obtained anterior segment parameters and the posterior corneal elevation value is presented in Table 2. The highest correlation rate for PCE was obtained by ACE (r = 0.642) in the control group. In the keratoconus group, the highest correlation rates were obtained by ACE (r = 0.881), SAI (r = 0.756), and DSI (r = 0.713). There was a negative

Table 2 Correlation of posterior corneal elevation with other corneal parameters for normal and keratoconic patients. PCE (␮m)

Keratoconus

Control

r-value

P-value

r-value

P-value

ACD (mm) ACE (␮m) SimKavg (D) Kavg (D) MK (D) TCT (␮m) CCT (␮m) IS SAI SRI IAI DSI OSI CSI ACP

−0.155 0.881 0.396 −0.337 0.396 −0.374 −0.266 0.599 0.756 0.458 0.440 0.713 0.605 0.139 0.357

<0.001 <0.001 0.473 <0.001 0.997 0.233 0.121 0.145 0.002 0.002 0.004 0.056 0.003 <0.001 0.408

−0.280 0.642 0.055 −0.265 0.001 0.091 0.119 0.112 0.235 0.240 0.220 0.146 0.227 0.296 0.063

<0.001 <0.001 0.473 <0.001 0.997 0.233 0.121 0.145 0.002 0.002 0.004 0.056 0.003 <0.001 0.408

ACD, anterior chamber depth; ACE, anterior corneal elevation; CCT, central corneal thickness; SD, standard deviation; Kavg, average posterior corneal keratometry; MK, mean keratometric value; PCE, posterior corneal elevation; SimKavg, average anterior corneal keratometry; TCT, thinnest corneal thickness; I–S, difference between the inferior and superior corneal thicknesses in the central 3 mm area; SAI, surface asymmetry index; SRI, degree of regularity (spherical property) of corneal surface; IAI, irregular astigmatism index; DSI, differential sector index, the difference between the two 45◦ sectors with the highest mean keratometric difference; OSI, opposite sector index, the difference between the two opposite 45◦ sectors with the highest difference; CSI, center/surround index, the mean keratometric difference between the central 3 mm area and the 3–6 mm corneal ring; ACP, average corneal power, the mean keratometric difference within the central 3 mm area of the cornea.

Please cite this article in press as: Demir S, et al. Comparison of normal and keratoconic corneas by Galilei Dual-Scheimpflug Analyzer. Contact Lens Anterior Eye (2013), http://dx.doi.org/10.1016/j.clae.2013.04.001

G Model CLAE-624; No. of Pages 7 4

ARTICLE IN PRESS S. Demir et al. / Contact Lens & Anterior Eye xxx (2013) xxx–xxx

Fig. 1. Receiver operating characteristic (ROC) graph showing the sensitivity and specificity for the MK, SimKavg, and Kavg parameters. Because the largest area under the curve is belonged to the parameter of Kavg in the graph, Kavg is the better parameter for discrimination of the keratoconic cornea from normal. It is statistically followed by SimKavg and MK. Kavg, average posterior corneal keratometry; MK, mean keratometric value; SimKavg, average anterior corneal keratometry.

correlation between corneal PCE and ACD (r = −0.28 in the control group, r = −0.115 in the keratoconus group). The ROC analysis of all obtained data was performed. The parameters are presented in Fig. 1 for mean keratometry, SimKavg, and Kavg; in Fig. 2 for I–S, SAI, SRI, IAI, DSI, OSI, CSI, and ACP; and in Fig. 3 for TCT, CCT, ACD, ACE, and PCE. The graphical data was supplied by the data in Table 3. In these graphics, posterior corneal elevation is the most sensitive parameter for differentiating patients with

Fig. 3. ROC graph showing the sensitivity and specificity of the TCT, CCT, ACD, ACE, and PCE parameters. The PCE is the better parameter and is followed by the parameters of ACE and ACD for discrimination keratoconic corneas from the normal corneas. ACD, anterior chamber depth; ACE, anterior corneal elevation; CCT, central corneal thickness; SD, standard deviation; Kavg, average posterior corneal keratometry; MK, mean keratometric value; PCE, posterior corneal elevation; SimKavg, average anterior corneal keratometry; TCT, thinnest corneal thickness.

keratoconus from normal patients. The area under the ROC curve is highest for PCE (0.999), followed by SAI (0.998), and ACE (0.997). At a posterior corneal elevation value of 18.5 ␮m, the sensitivity and specificity in differentiating keratoconus patients from normal individuals were 98.5% and 98.3%, respectively. The sensitivity and specificity rates at different posterior corneal elevation values are presented in Table 4. 4. Discussion Several devices, including slit scanning (Orbscan, Bausch & Lomb, Rochester, NY), Scheimpflug imaging (Pentacam, Oculus Inc., Table 3 ROC analysis of diverse anterior segment parameters obtained by Galilei readings with area under the curve values (keratoconic versus control eyes).

Fig. 2. ROC graph showing the sensitivity and specificity for parameters used in differentiation of keratoconus obtained by Galilei. Among these parameters, the SAI is the better parameter for discrimination keratoconic corneas from normal corneas and it is followed by DSI and OSI parameters in ROC analysis. ACD, anterior chamber depth; ACE, anterior corneal elevation; CCT, central corneal thickness; SD, standard deviation; Kavg, average posterior corneal keratometry; MK, mean keratometric value; PCE, posterior corneal elevation; SimKavg, average anterior corneal keratometry; TCT, thinnest corneal thickness; I–S, difference between the inferior and superior corneal thicknesses in the central 3 mm area; SAI, surface asymmetry index; SRI, degree of regularity (spherical property) of corneal surface; IAI, irregular astigmatism index; DSI, differential sector index, the difference between the two 45◦ sectors with the highest mean keratometric difference; OSI, opposite sector index, the difference between the two opposite 45◦ sectors with the highest difference; CSI, center/surround index, the mean keratometric difference between the central 3 mm area and the 3–6 mm corneal ring; ACP, average corneal power, the mean keratometric difference within the central 3 mm area of the cornea.

Parameters

Area under the ROC curve

SD

P-value

MK (D) SimKavg (D) Kavg (D) I–S SAI SRI IAI DSI OSI CSI ACP TCT CCT ACD ACE PCE

0.984 0.985 0.989 0.968 0.998 0.942 0.960 0.989 0.987 0.918 0.985 0.053 0.096 0.435 0.997 0.999

0.008 0.008 0.006 0.015 0.001 0.026 0.019 0.006 0.007 0.032 0.009 0.019 0.026 0.050 0.002 0.001

<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.175 <0.001 <0.001

ACD, anterior chamber depth; ACE, anterior corneal elevation; ACP, average corneal power, the mean keratometric difference within the central 3 mm area of the cornea; CCT, central corneal thickness; CSI, center/surround index, the mean keratometric difference between the central 3 mm area and the 3–6 mm corneal ring; DSI, differential sector index, the difference between the two 45◦ sectors with the highest mean keratometric difference; IAI, irregular astigmatism index; I–S, difference between the inferior and superior corneal thicknesses in the central 3 mm area; Kavg, average posterior corneal keratometry; MK, mean keratometric value; OSI, opposite sector index, the difference between the two opposite 45◦ sectors with the highest difference; PCE, posterior corneal elevation; SAI, surface asymmetry index; SD, standard deviation; SimKavg, average anterior corneal keratometry; SRI, degree of regularity (spherical property) of corneal surface; TCT, thinnest corneal thickness.

Please cite this article in press as: Demir S, et al. Comparison of normal and keratoconic corneas by Galilei Dual-Scheimpflug Analyzer. Contact Lens Anterior Eye (2013), http://dx.doi.org/10.1016/j.clae.2013.04.001

ARTICLE IN PRESS

G Model CLAE-624; No. of Pages 7

S. Demir et al. / Contact Lens & Anterior Eye xxx (2013) xxx–xxx Table 4 Cut-off point, sensitivity and specificity values for posterior corneal elevation (keratoconic versus control eyes). Posterior corneal elevation cutoff point (␮m) −4 0.5 1.5 2.5 4.5 8.5 13 18.5a 23.5 26.5 34.5 37.5 a

Sensitivity (%) 100 100 100 100 100 100 100 98.5 97 95.5 88.1 85.1

Specificity (%) 0 8.1 27.3 37.8 65.1 90.7 97.1 98.3 98.8 98.8 100 100

Cutoff point.

Dutenhofen, Germany; Galilei, Ziemer Ophthalmic Systems AG, Port, Switzerland), very high frequency (VHF) ultrasound (Artemis, Ultralink LLC, St Petersburg, FL), and high-speed anterior segment optical coherence tomography (Visante, Carl Zeiss Meditech, Jena, Germany), are currently available for evaluating anterior segment imaging of the eye. Today, some devices provide information about both the anterior and posterior surfaces of the cornea and create three-dimensional corneal images from their software at the same time. The Scheimpflug imaging technique provides perfectly sharp and crisp images that include data from the anterior corneal surface to the posterior crystalline capsule [19,20]. Recent studies shown that posterior corneal surface parameters enable clinicians to provide a more sensitive means to identify keratoconus [6,21]. While the first technology to allow measurement of the posterior surface was the Orbscan slit-scanning device, the second was the Scheimpflug imaging devices [22]. Unlike the Orbscan, the Scheimpflug technique measures the posterior surface of cornea directly. The Pentacam imaging device is a commonly used tool for imaging the anterior segment of the eye today. It evaluates the elevation by taking measurements from 138,000 points, according to position and visual axis, in the anterior segment, and it also uses an algorithm for correcting the 45◦ camera viewing angle for reconstructing the posterior surface [20]. The Galilei imaging device, which recently became commercially available, uses a rotating dual-Scheimpflug camera to image the anterior segment of the eye. It includes two rotating cameras while the Pentacam has only one. The second camera corrects errors caused by patient eye movements. In the literature, there are many studies on distinguishing keratoconus from normal eyes using the Pentacam [6–8,12–14,23,24]. However, to the best of our knowledge, there are no reports comparing the measurement parameters of the keratoconic and normal eyes by GSA. It is known that the corneal thickness decreases in keratoconus patients. The decrease occurs particularly in the apex of the conic corneal elevation [1]. Because both methods (Pentacam and GSA) perform localization independent measurement, they may obtain more precise CCT measurements [5]. This feature does not require eye contact, and the high repeatability of the measurement of corneal thickness is an important advantage of the Scheimpflug method [25]. For differentiation of normal individuals from keratoconus patients, corneal thickness may be a useful marker. Previous work on corneal thickness has shown that the corneal thickness was significantly thinner in subclinical and symptomatic keratoconus patients than normal individuals [6,13]. Moreover, corneal thickness asymmetry between the right and left eyes may be an important marker, especially in the early stage of the disease [26]. Therefore, the measurements of both eyes are useful in the early

5

diagnosis of keratoconus. In our study, the TCTs measured by the GSA were 459.8 ± 43.8 and 545.9 ± 36.8 in keratoconic and myopic patients, respectively. The CCTs were 492.3 ± 37.0 and 557.3 ± 34.8, respectively, and both of the parameters were statistically different (P < 0.001). These findings are similar to findings in a study performed with the Pentacam by Emre et al. [12]. A number of studies confirmed that the anterior chamber depth increased in patients with keratoconus [7,12,23,27]. However, to the best of our knowledge, only one study did not find a statistically significant difference in the ACD between the patients with keratoconus and normal eyes [28]. For this reason, the ACD should have been higher in patients with keratoconus in our study. However, the keratoconus group had an ACD of 3.3 mm and the control group (myopic patients) had an ACD of 3.35 mm (P = 0.149) in this study. The possible reason for this situation is likely due to the control group consisting of myopic individuals. The vast majority of the studies in the literature were constituted of normal subjects as a control group to determine the ACD as diagnostic parameters in patients with keratoconus. The eyeballs with greater axial lengths had more myopic refractive error, flatter corneal curvatures, and greater ACD [29,30]. So, statistically insignificant differences may have resulted due to axial length differences between the two groups; because of it has not been confirmed by biometric measurements, there is a limitation of our study. The anterior corneal surface elevation (ACE), one of the more common parameters currently used in the diagnosis of keratoconus, is actually measured by merging the data of the Placido and Scheimpflug for the anterior surface. The corneal elevation is frequently determined in the inferior cornea and inferior temporal regions in the keratoconus eyes [31]. The ACE parameter is higher in the keratoconus patients than the normal patients, but the data is variable from the different anterior segment imaging methods [32]. In the study by Fam and Lim [33], Orbscan was used and it was found that 16.5 ␮m is the ACE cut-off point for the differentiation of keratoconus from normal eyes. In their study using Pentacam, Emre et al. [12] measured the ACE value as 33.4 ␮m for the keratoconus patients and 2.7 ␮m for the control group (P < 0.001). In our study, the ACE values were 29.5 ± 14.9 ␮m and 2.5 ± 2.7 ␮m for the keratoconus and the myopic control groups, respectively (P < 0.001). From this data, the results of our study are very similar to the data obtained by Emre et al. [12]. Due to the frequent use of scanning slit corneal topography (Orbscan) and Scheimpflug imaging systems (Pentacam and GSA) during the last ten years, the posterior corneal surface parameters have become usable, in addition to the anterior corneal parameters, in the evaluation of keratoconus patients [32–34]. The posterior corneal surface parameters obtained by Orbscan are derived from the anterior corneal surface data using a mathematical estimate [35]. Placido disk-based corneal topography can be affected by anterior corneal surface pathologies and collects the data by performing 20 cross-sectional scans in every segment [36]. It is known that the posterior corneal curvature data that was obtained by Orbscan is different from the real value in the patients who underwent LASIK surgery [36–38]. The values of the PCE obtained by the different methods when measuring the same individuals may be different. For example, in the study by Quisling et al. [39], they compared posterior surface measurements obtained with Orbscan and those with Pentacam for keratoconus patients. In their study, the curvature radius and thinnest corneal thickness values obtained by the two devices were similar for keratoconus patients, but the posterior corneal surface elevation was higher when measured by Pentacam. Recently, many studies pointed out the importance of the posterior corneal elevation parameter for discrimination of keratoconus from normal individuals. In a study by Rao et al. [40], using Orbscan they determined that the PCE limit value, used to differentiate keratoconus patients from normal individuals, is 40 ␮m. In a

Please cite this article in press as: Demir S, et al. Comparison of normal and keratoconic corneas by Galilei Dual-Scheimpflug Analyzer. Contact Lens Anterior Eye (2013), http://dx.doi.org/10.1016/j.clae.2013.04.001

G Model CLAE-624; No. of Pages 7

ARTICLE IN PRESS S. Demir et al. / Contact Lens & Anterior Eye xxx (2013) xxx–xxx

6

study by de Sanctis et al. [8], at the 35 ␮m cut-off point, the PCE had 97.3% sensitivity and 96.3% specificity in differentiating the keratoconic patients from the control group. Mihaltz et al. [6] performed a similar study using Pentacam, and found that the PCE was 95.1% sensitive and 94.3% specific at a 15.5 ␮m cutoff-point. As no studies of the dual-Scheimpflug system on keratoconic patients appear in the literature to date, the confidence rates of the PCE values in differentiation by GSA could not be assessed previously. In our study, the PCE values had a mean of 57.7 ± 25.8 ␮m for the keratoconus group and a mean of 5.25 ± 4.8 ␮m for the control group (P < 0.001). The area under the ROC curve was 0.999, the highest value of all the parameters. In our study, at the 18.5 ␮m cut-off point for the PCE value, the sensitivity was 98.5% and the specificity was 98.3%. From this data, the results of our study are very similar to the data obtained Mihaltz et al. [6]. This study is the first one that compares the I–S, SAI, SRI, IAI, DSI, OSI, CSI, and ACP parameters, automatically used to evaluate the possibility of keratoconus by the GSA, for the control and keratoconus groups. All the parameters were statistically different for the control and keratoconus groups (P < 0.001). Among these parameters, the highest ROC value was obtained by the SAI (0.998), followed by the DSI (0.989), OSI (0.987), ACP (0.985), and I–S (0.968) (Table 4). 5. Conclusion In conclusion, posterior corneal surface elevation was the most significant parameter in the discrimination of keratoconus patients. It was also observed that an 18.5 ␮m cut-off point for the PCE was 98.5% sensitive and 98.3% specific in differentiating keratoconic corneas from myopic eyes. The specific parameters (indices) included in the Galilei software for the prediction of keratoconus were found statistically different in two groups. The SAI value, in particular, was found to be the second most important parameter for the differentiation of patients, following the posterior corneal elevation. Conflict of interest This study has no financial support and the authors report no declarations of interest. References [1] Rabinowitz YS. Keratoconus. Survey of Ophthalmology 1998;42:297–319. [2] Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Survey of Ophthalmology 1984;28:293–322. [3] Romero-Jimenez M, Santodomingo-Rubido J, Wolffsohn JS. Keratoconus: a review. Contact Lens & Anterior Eye 2010;33:157–66, quiz 205. [4] Wilson SE. Cautions regarding measurements of the posterior corneal curvature. Ophthalmology 2000;107:1223. [5] de Sanctis U, Missolungi A, Mutani B, Richiardi L, Grignolo FM. Reproducibility and repeatability of central corneal thickness measurement in keratoconus using the rotating Scheimpflug camera and ultrasound pachymetry. American Journal of Ophthalmology 2007;144:712–8. [6] Mihaltz K, Kovacs I, Takacs A, Nagy ZZ. Evaluation of keratometric, pachymetric, and elevation parameters of keratoconic corneas with pentacam. Cornea 2009;28:976–80. [7] Edmonds CR, Wung SF, Pemberton B, Surrett S. Comparison of anterior chamber depth of normal and keratoconus eyes using Scheimpflug photography. Eye & Contact Lens 2009;35:120–2. [8] de Sanctis U, Loiacono C, Richiardi L, Turco D, Mutani B, Grignolo FM. Sensitivity and specificity of posterior corneal elevation measured by Pentacam in discriminating keratoconus/subclinical keratoconus. Ophthalmology 2008;115:1534–9. [9] Sy ME, Ramirez-Miranda A, Zarei-Ghanavati S, Engle J, Danesh J, Hamilton DR. Comparison of posterior corneal imaging before and after LASIK using dual rotating scheimpflug and scanning slit-beam corneal tomography systems. Journal of Refractive Surgery 2013;29:96–101. [10] Aramberri J, Araiz L, Garcia A, Illarramendi I, Olmos J, Oyanarte I, et al. Dual versus single Scheimpflug camera for anterior segment analysis: precision and agreement. Journal of Cataract and Refractive Surgery 2012;38:1934–49.

[11] Yeter V, Sönmez B, Beden U. Comparison of central corneal thickness measurements by Galilei Dual-Scheimpflug analyzer® and ultrasound pachymeter in myopic eyes. Ophthalmic Surgery, Lasers and Imaging 2012;43: 128–34. [12] Emre S, Doganay S, Yologlu S. Evaluation of anterior segment parameters in keratoconic eyes measured with the Pentacam system. Journal of Cataract and Refractive Surgery 2007;33:1708–12. [13] Ucakhan OO, Cetinkor V, Ozkan M, Kanpolat A. Evaluation of Scheimpflug imaging parameters in subclinical keratoconus, keratoconus, and normal eyes. Journal of Cataract and Refractive Surgery 2011;37:1116–24. [14] Pinero DP, Alio JL, Aleson A, Escaf M, Miranda M. Pentacam posterior and anterior corneal aberrations in normal and keratoconic eyes. Clinical & Experimental Optometry 2009;92:297–303. [15] Menassa N, Kaufmann C, Goggin M, Job OM, Bachmann LM, Thiel MA. Comparison and reproducibility of corneal thickness and curvature readings obtained by the Galilei and the Orbscan II analysis systems. Journal of Cataract and Refractive Surgery 2008;34:1742–7. [16] Salouti R, Nowroozzadeh MH, Zamani M, Fard AH, Niknam S. Comparison of anterior and posterior elevation map measurements between 2 Scheimpflug imaging systems. Journal of Cataract and Refractive Surgery 2009;35:856–62. [17] Wegener A, Laser-Junga H. Photography of the anterior eye segment according to Scheimpflug’s principle: options and limitations – a review. Clinical and Experimental Ophthalmology 2009;37:144–54. [18] Choi JA, Kim MS. Progression of keratoconus by longitudinal assessment with corneal topography. Investigative Ophthalmology and Visual Science 2012;53:927–35. [19] Kopacz D, Maciejewicz P, Kecik D. Pentacam – the new way for anterior eye segment imaging and mapping. Klinika Oczna 2005;107:728–31. [20] Konstantopoulos A, Hossain P, Anderson DF. Recent advances in ophthalmic anterior segment imaging: a new era for ophthalmic diagnosis? British Journal of Ophthalmology 2007;91:551–7. [21] Arbelaez MC, Versaci F, Vestri G, Barboni P, Savini G. Use of a support vector machine for keratoconus and subclinical keratoconus detection by topographic and tomographic data. Ophthalmology 2012;119:2231–8. [22] Swartz T, Marten L, Wang M. Measuring the cornea: the latest developments in corneal topography. Current Opinion in Ophthalmology 2007;18: 325–33. [23] Kovacs I, Mihaltz K, Nemeth J, Nagy ZZ. Anterior chamber characteristics of keratoconus assessed by rotating Scheimpflug imaging. Journal of Cataract and Refractive Surgery 2010;36:1101–6. [24] Szalai E, Berta A, Hassan Z, Modis Jr L. Reliability and repeatability of swept-source Fourier-domain optical coherence tomography and Scheimpflug imaging in keratoconus. Journal of Cataract and Refractive Surgery 2012;38:485–94. [25] Ucakhan OO, Ozkan M, Kanpolat A. Corneal thickness measurements in normal and keratoconic eyes: Pentacam comprehensive eye scanner versus noncontact specular microscopy and ultrasound pachymetry. Journal of Cataract and Refractive Surgery 2006;32:970–7. [26] Khachikian SS, Belin MW, Ciolino JB. Intrasubject corneal thickness asymmetry. Journal of Refractive Surgery 2008;24:606–9. [27] Fontes BM, Ambrosio Junior R, Jardim D, Velarde GC, Nose W. Ability of corneal biomechanical metrics and anterior segment data in the differentiation of keratoconus and healthy corneas. Arquivos Brasileiros de Oftalmologia 2010;73:333–7. ˜ [28] Montalbán R, Alió JL, Javaloy J, Pinero DP. Intrasubject repeatability in keratoconus-eye measurements obtained with a new Scheimpflug photography-based system. Journal of Cataract and Refractive Surgery 2013;39:211–8. [29] Chang SW, Tsai IL, Hu FR, Lin LL, Shih YF. The cornea in young myopic adults. British Journal of Ophthalmology 2001;85:916–20. [30] Chen MJ, Liu YT, Tsai CC, Chen YC, Chou CK, Lee SM. Relationship between central corneal thickness, refractive error, corneal curvature, anterior chamber depth and axial length. Journal of the Chinese Medical Association 2009;72:133–7. [31] Rabinowitz YS, Rasheed K. KISA% index: a quantitative videokeratography algorithm embodying minimal topographic criteria for diagnosing keratoconus. Journal of Cataract and Refractive Surgery 1999;25:1327–35. [32] Arntz A, Duran JA, Pijoan JI. Subclinical keratoconus diagnosis by elevation topography. Archivos de la Sociedad Espanola de Oftalmologia 2003;78:659–64. [33] Fam HB, Lim KL. Corneal elevation indices in normal and keratoconic eyes. Journal of Cataract and Refractive Surgery 2006;32:1281–7. [34] Sonmez B, Doan MP, Hamilton DR. Identification of scanning slit-beam topographic parameters important in distinguishing normal from keratoconic corneal morphologic features. American Journal of Ophthalmology 2007;143:401–8. [35] Cairns G, McGhee CN. Orbscan computerized topography: attributes, applications, and limitations. Journal of Cataract and Refractive Surgery 2005;31:205–20. [36] Ho T, Cheng AC, Rao SK, Lau S, Leung CK, Lam DS. Central corneal thickness measurements using Orbscan II, Visante, ultrasound, and Pentacam pachymetry after laser in situ keratomileusis for myopia. Journal of Cataract and Refractive Surgery 2007;33:1177–82. [37] Cheng AC, Ho T, Lau S, Lam DS. Evaluation of the apparent change in posterior corneal power in eyes with LASIK using Orbscan II with magnification compensation. Journal of Refractive Surgery 2009;25:221–8.

Please cite this article in press as: Demir S, et al. Comparison of normal and keratoconic corneas by Galilei Dual-Scheimpflug Analyzer. Contact Lens Anterior Eye (2013), http://dx.doi.org/10.1016/j.clae.2013.04.001

G Model CLAE-624; No. of Pages 7

ARTICLE IN PRESS S. Demir et al. / Contact Lens & Anterior Eye xxx (2013) xxx–xxx

[38] Lopez-Miguel A, Nieto JC, Diez-Cuenca M, Pinero DP, Maldonado MJ. Agreement of non-contact pachymetry after LASIK: comparison of combined scanning-slit/Placido disc topography and specular microscopy. Eye (London) 2010;24:1064–70. [39] Quisling S, Sjoberg S, Zimmerman B, Goins K, Sutphin J. Comparison of Pentacam and Orbscan IIz on posterior curvature topography

7

measurements in keratoconus eyes. Ophthalmology 2006;113:1629– 32. [40] Rao SN, Raviv T, Majmudar PA, Epstein RJ. Role of Orbscan II in screening keratoconus suspects before refractive corneal surgery. Ophthalmology 2002;109:1642–6.

Please cite this article in press as: Demir S, et al. Comparison of normal and keratoconic corneas by Galilei Dual-Scheimpflug Analyzer. Contact Lens Anterior Eye (2013), http://dx.doi.org/10.1016/j.clae.2013.04.001