Keratoconus (KC) is a noninflammatory ectatic corneal dystrophy characterized by a usually progressive corneal thinning that results in corneal steepening, protrusion, irregular astigmatism, and gradual impairment of vision [
Evaluation of keratoconic and normal eyes to determine all tomographic parameters including keratoconus indices, pachymetric graph values, and back difference elevation values of the corneas may help to identify at-risk corneas.
The purpose of our study was to evaluate and compare the anterior and posterior corneal surface parameters, keratoconus indices, thickness profile data, and data from enhanced elevation maps of keratoconic and normal corneas with the Pentacam Scheimpflug corneal tomography and to determine the sensitivity and specificity of these parameters in discriminating keratoconus from normal eyes.
The protocol of this retrospective clinic-based observational study of 656 eyes of 338 patients diagnosed with keratoconus and 513 eyes of 268 healthy control subjects adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee, Marmara University Hospital, Istanbul, Turkey. All patients included in the study were informed about the purpose of the study and provided informed consent. Subjects were recruited from consecutive patients who were admitted to the university hospital (Marmara University Hospital, Istanbul, Turkey) or the private eye hospital (Birinci Eye Hospital, Istanbul, Turkey) for ocular examination between September 2013 and April 2014.
Exclusion criteria were previous eye trauma, corneal or intraocular surgery, glaucoma, corneal scarring, severe eye dryness, pregnancy or nursing, current corneal infections, and the use of topical medications. Soft contact lens users were included in the study after discontinuation of lens wear for at least 7 days.
Keratoconus was diagnosed mainly on the basis of clinical slit-lamp findings, keratometry, and associated characteristic topographic patterns. Eyes were considered normal if they had no ocular pathology, no previous ocular surgery, and no irregular corneal pattern.
A comprehensive ocular examination including Scheimpflug corneal tomography was performed on all eyes. Measurements were taken with a high-resolution imaging system which uses a rotating Scheimpflug camera (Pentacam, Oculus Optikgeräte GmbH, Wetzlar, Germany) and a monochromatic slit-light source that rotate together around the optical axes of the eye for measuring anterior segment topography. The Pentacam provides a multitude of corneal topographic (keratometric), topometric, tomographic, and pachymetric data. The room lights were switched off for all examinations to get a reflex-free image. The subjects were asked to position themselves, blink a couple of times, and fixate on the black target in the center of the blue fixation beam. Patients were instructed to close their eyes between shots for at least 10 seconds to moisten the eyes. The images were obtained with the automatic mode. The camera was rotated 180°, obtaining 25 slit images of the anterior segment, and generated a three-dimensional model of the anterior eye. Eye movement of the subject was constantly monitored by the system, and quality factor was automatically evaluated. Only the scan results with quality factor (QS) of >95% were saved.
Parameters were derived from topographic, topometric, and BAD maps (Figures
(a) Topographic, (b) topometric, and (c) Belin-Ambrósio enhanced ectasia display maps of the Pentacam.
Corneal thickness was defined as the thinnest point in the corneal thickness map. Corneal volume is reported as the volume of the cornea in a diameter of 10 mm, centered on the anterior corneal apex. Anterior chamber depth was defined as the distance from the corneal endothelium to the anterior surface of the lens capsule. The anterior chamber volume is calculated from endothelium down to iris and lens over a 12 mm diameter centered on the anterior corneal apex. The default angle displayed is the smallest angle in the horizontal position calculated from the Scheimpflug image. For elevation data measurement, the best fit sphere served as a reference body using the float option and the diameter of the reference surface was 8 mm. Front and back elevation difference values were taken as the differential changes in corneal elevation between the best fit sphere (BFS) and the enhanced BFS obtained with the BAD display software. Progression index is calculated as the average progression value at the different pachymetric rings, referenced to the mean curve.
Spherical equivalent (SE: sphere + half the cylinder) values, in diopters (D), were calculated from cycloplegic refraction for each patient. The asphericity data provided by the Pentacam was taken from 8 mm central cornea with reference to the anterior corneal apex.
Eyes with keratoconus were compared with normal corneas in separate series of analyses. All numerical results were entered into a database, and statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 16.0. ROC curves were used to determine the overall predictive accuracy of the test as described by the area under the curve. For the output values of the discriminant functions tested, the area under the ROC curve (AUROC), sensitivity (true positive/(true positive false negative)), specificity (true negative/(true negative false positive)), accuracy ((true positive true negative)/total number of cases), and cutoff value were calculated.
The AUROC curve is a plot of sensitivity against 1 − specificity, that is, true positives versus false positives. This area ranges from 1 (100%) representing perfect discrimination to 0.5 (50%) representing discrimination being no better than chance. In between that range, 0.90–1 represent excellent discrimination, 0.80–0.90 good, 0.70–0.80 fair, 0.60–0.70 poor, and 0.50–0.60 very poor [
In the normal group, the study involved 513 eyes of 268 subjects with a mean age of 32.99 years, ranging from 8 to 74 years old. One hundred nine (48.1%) of subjects were male and 139 (51.9%) were female. In the keratoconus group, the study involved 656 eyes of 338 subjects with a mean age of 31.18 years, ranging from 13 to 64 years old. Two hundred fourteen (63.2%) of subjects were male and 124 (36.8%) were female. The mean spherical refraction of normal eyes was −0.88 D.
The two groups did not differ significantly with regard to age and gender (
The mean Pentacam parameters and the differences between keratoconus and normal subjects are shown in Table
Mean Pentacam parameters and the difference between keratoconus and normal eyes.
Pentacam parameter | KC |
Control |
|
---|---|---|---|
Topographic map | |||
Kflat (Ant.) | 46.37 ± 4.75 |
43.03 ± 1.57 |
<0.001 |
Ksteep (Ant.) | 49.41 ± 5.56 |
44.17 ± 1.58 |
<0.001 |
Kmean (Ant.) | 47.80 ± 5.06 |
43.60 ± 1.52 |
<0.001 |
Kmax | 54.11 ± 8.34 |
44.67 ± 2.17 |
<0.001 |
Astigmatism (Ant.) | 3.05 ± 1.97 |
1.13 ± 0.86 |
<0.001 |
Asphericity (Ant.) | −0.78 ± 0.54 |
−0.34 ± 0.12 |
<0.001 |
Kflat (Post.) | −6.82 ± 0.96 |
−6.13 ± 0.26 |
<0.001 |
Ksteep (Post.) | −7.39 ± 1.08 |
−6.41 ± 0.28 |
<0.001 |
Kmean (Post.) | −7.09 ± 0.95 |
−6.27 ± 0.24 |
<0.001 |
Astigmatism (Post.) | 0.71 ± 0.44 |
0.31 ± 0.17 |
<0.001 |
Asphericity (Post.) | −0.81 ± 0.52 |
0.35 ± 0.15 |
<0.001 |
TCT | 456.76 ± 54.53 |
545.94 ± 36.76 |
<0.001 |
Cornea Vol | 57.08 ± 3.71 |
60.70 ± 4.06 |
<0.001 |
AC Vol | 195.90 ± 35.12 |
175.04 ± 42.37 |
<0.001 |
ACD | 3.32 ± 0.35 |
3.00 ± 0.41 |
<0.001 |
AC Angle | 39.20 ± 6.59 |
37.01 ± 8.13 |
<0.001 |
Topometric map | |||
ISV | 76.10 ± 42.42 |
17.70 ± 6.67 |
<0.001 |
IVA | 0.77 ± 0.44 |
0.12 ± 0.058 |
<0.001 |
KI | 1.19 ± 0.13 |
1.01 ± 0.019 |
<0.001 |
CKI | 1.05 ± 0.057 |
1.00 ± 0.005 |
<0.001 |
IHA | 22.64 ± 18.96 |
4.13 ± 4.60 |
<0.001 |
IHD | 0.75 ± 0.070 |
0.011 ± 0.019 |
<0.001 |
Rmin | 6.35 ± 0.81 |
7.55 ± 0.27 |
<0.001 |
HOR Q | −0.85 ± 1.50 |
−0.33 ± 0.14 |
<0.001 |
VERT Q | −1.01 ± 3.66 |
−0.35 ± 0.16 |
<0.001 |
BAD display | |||
Front diff. | 16.28 ± 12.14 |
3.59 ± 2.43 |
<0.001 |
Back diff. | 35.74 ± 25.95 |
5.64 ± 3.50 |
<0.001 |
Dist.Apex-Th | 0.84 ± 0.28 |
0.82 ± 0.23 |
0.349 |
F.Ele.Th | 20.53 ± 14.33 |
2.29 ± 1.80 |
<0.001 |
B.Ele.Th | 47.39 ± 28.52 |
6.41 ± 3.83 |
<0.001 |
ProgMin | 1.74 ± 1.11 |
0.69 ± 0.12 |
<0.001 |
ProgMax | 3.20 ± 3.24 |
1.22 ± 0.20 |
<0.001 |
ProgAvg | 2.26 ± 1.88 |
0.96 ± 0.13 |
<0.001 |
ARTmax | 187.74 ± 91.00 |
457.83 ± 86.44 |
<0.001 |
Df | 9.63 ± 8.62 |
0.22 ± 1.14 |
<0.001 |
Db | 8.34 ± 10.57 |
0.04 ± 0.91 |
<0.001 |
Dp | 9.13 ± 12.29 |
0.35 ± 1.89 |
<0.001 |
Dt | 3.02 ± 2.90 |
−0.15 ± 1.02 |
<0.001 |
Da | 2.72 ± 0.81 |
0.27 ± 0.77 |
<0.001 |
D | 8.39 ± 6.22 |
0.93 ± 0.66 |
<0.001 |
All parameters derived from the three maps showed statistically significant difference between keratoconic and normal eyes except the distance from corneal apex to thinnest location parameter (
Table
ROC curve analysis for the keratoconus eyes versus normal eyes.
Parameters | AUC | SE | 95% CI |
|
Cutoff | Sensitivity | Specificity |
---|---|---|---|---|---|---|---|
Topographic map | |||||||
Kflat (Ant.) | 0.755 | 0.014 | 0.728–0.783 | <0.001 | 45.15 | 0.500 | 0.915 |
Ksteep (Ant.) | 0.857 | 0.011 | 0.836–0.878 | <0.001 | 46.45 | 0.685 | 0.929 |
Kmean (Ant.) | 0.820 | 0.012 | 0.796–0.844 | <0.001 | 45.25 | 0.646 | 0.863 |
Kmax | |||||||
Astigmatism (Ant.) | 0.815 | 0.013 | 0.791–0.840 | <0.001 | 1.65 | 0.733 | 0.816 |
Asphericity (Ant.) | 0.795 | 0.014 | 0.768–0.721 | <0.001 | −0.565 | 0.974 | 0.618 |
Kflat (Post.) | 0.757 | 0.014 | 0.729–0.785 | <0.001 | −6.55 | 0.939 | 0.516 |
Ksteep (Post.) | 0.842 | 0.012 | 0.819–0.865 | <0.001 | −6.85 | 0.941 | 0.674 |
Kmean (Post.) | 0.819 | 0.012 | 0.795–8.44 | <0.001 | −6.65 | 0.945 | 0.631 |
Kmax | 0.928 | 0.008 | 0.914–0.943 | <0.001 | 47.05 | 0.839 | 0.935 |
Astigmatism (Post.) | 0.802 | 0.013 | 0.776–0.828 | <0.001 | 0.45 | 0.708 | 0.828 |
Asphericity (Post.) | 0.780 | 0.014 | 0.752–0.807 | <0.001 | −0.555 | 0.892 | 0.678 |
TCT | 0.915 | 0.08 | 0.899–0.932 | <0.001 | 506.5 | 0.890 | 0.832 |
Cornea Vol | 0.713 | 0.015 | 0.701–0.760 | <0.001 | 58.55 | 0.695 | 0.687 |
AC Vol | 0.650 | 0.017 | 0.617–0.683 | <0.001 | 169.5 | 0.769 | 0.452 |
ACD | 0.724 | 0.015 | 0.695–0.754 | <0.001 | 3.155 | 0.703 | 0.631 |
AC Angle | 0.584 | 0.017 | 0.550–0.618 | <0.001 | 33.25 | 0.854 | 0.278 |
Topometric map | |||||||
ISV | 0.954 | 0.006 | 0.942–0.966 | <0.001 | 31.5 | 0.878 | 0.962 |
IVA | 0.963 | 0.006 | 0.952–0.974 | <0.001 | 0.255 | 0.913 | 0.964 |
KI | 0.970 | 0.005 | 0.960–0.979 | <0.001 | 1.055 | 0.910 | 0.982 |
CKI | 0.824 | 0.013 | 0.798–0.849 | <0.001 | 1.015 | 0.727 | 0.982 |
IHA | 0.883 | 0.10 | 0.863–0.902 | <0.001 | 8.65 | 0.757 | 0.886 |
IHD | 0.951 | 0.006 | 0.938–0.963 | <0.001 | 0.0175 | 0.900 | 0.890 |
Rmin | 0.929 | 0.008 | 0.914–0.943 | <0.001 | 7.085 | 0.968 | 0.807 |
HOR Q | 0.811 | 0.13 | 0.895–0.837 | <0.001 | −0.495 | 0.896 | 0.711 |
VERT Q | 0.719 | 0.015 | 0.689–0.750 | <0.001 | −0.625 | 0.951 | 0.545 |
BAD maps | |||||||
Front diff. | 0.910 | 0.008 | 0.894–0.926 | <0.001 | 8.5 | 0.716 | 1 |
Back diff. | 0.954 | 0.006 | 0.942–0.966 | <0.001 | 12.5 | 0.873 | 0.961 |
Dist.Apex-Th | 0.512 | 0.17 | 0.478–0.545 | 0.499 | 0.955 | 0.314 | 0.760 |
F.Ele.Th | 0.959 | 0.006 | 0.947–0971 | <0.001 | 5.5 | 0.913 | 0.974 |
B.Ele.Th | 0.967 | 0.005 | 0.956–0.977 | <0.001 | 13.5 | 0.932 | 0.949 |
ProgMin | 0.935 | 0.008 | 0.921–0.950 | <0.001 | 0.925 | 0.854 | 0.972 |
ProgMax | 0.964 | 0.005 | 0.953–0.974 | <0.001 | 1.675 | 0.888 | 0.978 |
ProgAvg | 0.955 | 0.006 | 0.943–0.968 | <0.001 | 1.185 | 0.914 | 0.951 |
ARTmax | 0.961 | 0.006 | 0.949–0.972 | <0.001 | 311 | 0.966 | 0.907 |
Df | 0.949 | 0.006 | 0.937–0.962 | <0.001 | 2.575 | 0.847 | 0.972 |
Db | 0.957 | 0.006 | 0.946–0.968 | <0.001 | 1.72 | 0.882 | 0.943 |
Dp | 0.954 | 0.006 | 0.942–0.967 | <0.001 | 1.855 | 0.919 | 0.951 |
Dt | 0.914 | 0.008 | 0.897–0.930 | <0.001 | 0.955 | 0.830 | 0.888 |
Da | 0.964 | 0.006 | 0.953–0.975 | <0.001 | 1.62 | 0.905 | 0.968 |
D | 0.972 | 0.005 | 0.963–0.982 | <0.001 | 2.615 | 0.932 | 0.990 |
AUC: Area Under ROC Curve.
SE: Standard error.
CI: Confidence Interval.
Out of 40 parameters derived from the topographic, topometric, and BAD maps 2 (TCT, AUROC 0.915; Kmax, AUROC 0.928), 5 (ISV, AUROC 0.954; IVA, AUROC 0.963; KI, AUROC 0.970; IHD, AUROC 0.951; Rmin, AUROC 0.929), and 14 (FDE, AUROC 0.910 BDE, AUROC 0.954; F.Ele.Th, AUROC 0.959; B.Ele.Th, AUROC 0.967; ProgMin, AUROC 0.935; ProgMax, AUROC 0.964; ProgAvg, AUROC 0.955; ARTmac, AUROC 0.961; Df, AUROC 0.949; Db, AUROC 0.957; Dp, AUROC 0.954; Dt, AUROC 0.914; Da, AUROC 0.964; D, AUROC 0.972) parameters, respectively, showed excellent AUROC values in discriminating keratoconic eyes from normal ones.
Among these parameters IVA, KI, F.Ele.Th, B.Ele.Th, ARTmac, Dp, Da, and D showed excellent (>90%) sensitivity and specificity in addition to excellent AUROC. The cutoff points derived from the ROC curve analysis were 0.255 for IVA, 1.055 for KI, 5.5 for F.Ele.Th, 13.5 for B.Ele.Th, 311 for ARTmac, 1.855 for Dp, 1.62 for Da, and 2.615 for D.
This retrospective study analyzed the efficacy of the parameters derived from the anterior and posterior corneal surfaces, keratoconus indices, thickness profile data, and data from enhanced elevation maps in discriminating eyes with KC from normal eyes. All parameters derived from the three maps showed statistically significant difference between keratoconus and normal group except the parameter of distance between thinnest point and apex. Previous studies found a mean distance between the apex and the thinnest point to range from 0.52 to 1.01 mm in healthy eyes and 0.78 mm in keratoconus eyes [
We further did ROC analysis to evaluate the predictive accuracy of these parameters in differentiating KC from normal corneas. Forty parameters derived from three maps were analysed. Out of 15 parameters from the topography maps thinnest corneal thickness (TCT) and Kmax showed excellent predictive accuracy. Being a well-known pathophysiological feature of KC, corneal thickness is an important marker for both detection of KC and the severity level of the disease [
Nine parameters were studied from the topometric map and 5 of them showed excellent discrimination of keratoconus. These anterior surface topometric indices were ISV, IVA, KI, IHD, and Rmin. Table
Abnormal topometric indices values of the manufacturer’s user manual and the study.
Index | Abnormal values of manufacturer’s user manual | Abnormal values of the study |
---|---|---|
ISV | >31.5 | |
IVA | 0.28 | >0.255 |
KI | >1.07 | >1.055 |
CKI | 1.03 | >1.015 |
IHA | 19 | >8.65 |
IHD | 0.014 | >0.0175 |
Rmin | <6.71 | <7.085 |
Fifteen parameters were studied from the BAD and 14 of them showed excellent discrimination. Difference in anterior and posterior elevation (FDE, BDE), F.Ele.Th, B.Ele.Th, ProgMin, ProgMax, ProgAvg, ARTmac, Df, Db, Dp, Dt, Da, and D showed excellent predictive accuracy. The BAD is an integrated display in the Pentacam that combines elevation based and comprehensive pachymetric corneal evaluation in an all-inclusive display. The BAD displays each parameter and individually reports them as a standard deviation and then reports a final overall reading that is based on a regression analysis to maximize the separation of normal corneas from those with keratoconus [
Corneal thickness spatial profile, percentage increase in thickness, percentage increase, and D parameters had high predictive accuracies in discriminating keratoconus from normal eyes.
Ambrósio et al. introduced the analysis of corneal thickness spatial profiles and demonstrated significant differences in absolute thickness and percentage thickness increase as a function of distance from the thinnest point between normal and KC eyes [
D parameters compute the deviation from normal indices for the enhanced front and back elevations, for the thinnest value and for the pachymetric distributions. We found that all D parameters showed excellent accuracy in the discrimination of keratoconus.
Among all parameters studied, only IVA, KI, F.Ele.Th, B.Ele.Th, ARTmax, Dp, Da, and D showed excellent (>90%) sensitivity and specificity in addition to excellent AUROC level.
One limitation of our study is that forme fruste keratoconus patients were not separated from keratoconus patients, so our work gives no threshold value for the detection of this condition.
In conclusion, this study aimed to evaluate the effectiveness of a large number of Pentacam parameters in the diagnosis of keratoconus in a fairly large sample size showing that the predictive accuracy of topographic, topometric, and BAD parameters was overall high but that the parameters of index of vertical asymmetry, keratoconus index, front and back elevation at the thinnest point, ART, and D values were the most sensitive and specific parameters for the diagnosis of keratoconus. These results may suggest that rather than relying on a single map, comprehensive analysis of topography, topometric indices, pachymetric data, and corneal height data in the Belin-Ambrósio enhanced ectasia display may provide useful information for improving the accuracy of keratoconus diagnosis and screening refractive candidates in a clinical setting.
Keratometry
Thinnest corneal thickness
Cornea volume
Anterior chamber volume
Anterior chamber depth
Anterior chamber angle
Index of surface variance
Index of vertical asymmetry
Keratoconus index
Center keratoconus index
Index of height asymmetry
Index of height decentration
Minimum sagittal curvature
Horizontal mean asphericity
Vertical mean asphericity
Subtraction enhanced FBFS from FBFSc
Subtraction enhanced BBFS from BBFS
Distance from corneal apex to thinnest location
Front elevation at thinnest location
Back elevation at thinnest location
Progress index
Ambrósio Relational Thickness
Deviation of front elevation difference map
Deviation of back elevation difference map
Deviation of average pachymetric progression
Deviation of minimum thickness
Deviation of ARTmax
Total deviation value.
The authors declare that there is no conflict of interests regarding the publication of this paper. The authors do not have any proprietary interest in the products and drugs mentioned in this paper.