Purpose
To investigate the magnitude, with-the-rule (WTR) or against-the-rule (ATR) orientation, and vector components (Jackson astigmatic vectors [J 0 and J 45 ] and blurring strength) of the anterior and posterior corneal astigmatism (ACA and PCA) in patients with keratoconus (KC) in a retrospective study, and to try to find suitable cutoff points for ACA and PCA in an attempt to discriminate KC from normal corneas.
Design
Retrospective age- and sex-matched case-control study.
Methods
Using the Pentacam images, the aforementioned parameters were compared between 1273 patients with KC and 1035 normal participants.
Results
The mean magnitude of the ACA and PCA was 4.49 ± 2.16 diopter (D) and 0.90 ± 0.43 D, respectively. The dominant astigmatism orientation of the ACA was ATR in KC patients and WTR in normal participants ( P < .001), while for the PCA it was WTR in KC patients and ATR in normal participants ( P < .001). There was a significant agreement between the axis orientations of ACA and PCA in KC patients (ĸ = 0.077, P < .001), but not in the normal group ( P = .626). ACA and PCA magnitude, M, J 0 , J 45 , and blur significantly increased by increasing KC severity. There was a trend for increasing anterior ATR and posterior WTR, and decreasing oblique astigmatism on both corneal surfaces by increasing the KC severity according to the Amsler-Krumeich classification. A cutoff value of 1.8 D for ACA had 90.2% sensitivity and specificity, and that of 0.4 D for PCA had 89.5% sensitivity and 85.0% specificity for discriminating KC from normal corneas.
Conclusion
Our findings can help clinicians in the diagnosis of KC and lens manufacturers in designing suitable contact or intraocular lenses.
Keratoconus (KC) is a progressive, usually bilateral ectatic corneal disorder, characterized by corneal thinning and protrusion. KC starts at puberty and progresses to the third or fourth decade of life, causing myopia and astigmatism, which results in severe vision distortion and sometimes even blindness. Astigmatism is a refractive error that is mostly caused by toricity of the anterior corneal surface leading to visually significant optical aberration. Both the anterior and posterior corneal surfaces contribute to the total corneal astigmatism. Recently, the direct and quantitative measurement of the posterior corneal measurements in a clinical setting has been possible with new imaging technologies such as slit-scanning, Scheimpflug, or optical coherence devices.
Assessment of the corneal astigmatism plays an important role in vision correction procedures such as rigid gas-permeable lens prescription or intraocular lens (IOL) implantation in KC patients. Ho and associates reported that neglecting the posterior corneal astigmatism may result in significant deviation in the estimation of the corneal astigmatism. There are several studies evaluating anterior corneal astigmatism in KC patients ; however, a few studies evaluated the magnitude and orientation of the posterior corneal astigmatism in patients with KC. Moreover, several studies tried to differentiate between KC and normal corneas by means of corneal astigmatism and suggested various cutoff points with different sensitivity and specificity. But the results are inconclusive.
In the current study, we aimed to investigate the magnitude, orientation, and vector components of the anterior and posterior corneal astigmatism in patients with KC in comparison with normal corneas and according to different KC severity stages. Furthermore, we tried to find a suitable cutoff point for the anterior and posterior corneal astigmatism that could discriminate between KC and normal corneas with the highest sensitivity, specificity, and accuracy.
Methods
A retrospective age- and sex-matched case-control study was conducted in Zarrinbakhsh Eye Clinic, Tehran, Iran, reviewing the documents of the patients diagnosed with KC who attended the clinic from 2010 to 2015. This study was in accordance with the tenets of the Declaration of Helsinki and the Institutional Review Board (IRB) and ethics committee of our clinic approved the study. Since our study was a retrospective chart review, the IRB of our clinic waived the requirement of obtaining informed consent from the participants.
The diagnosis of KC was based on the clinical characteristic signs, such as Fleischer ring, Vogt striae, and stromal scar, using slit-lamp examinations and also corneal topography evaluation using Pentacam (OCULUS Optikgerate GmbH, Wetzlar, Germany). For the control group, a number of age- and sex-matched subjects who primarily attended the clinic for laser in situ keratomileusis, and who did not fulfill the diagnostic criteria of the KC or were not KC suspect based on slit-lamp examination and Pentacam imaging, were consecutively selected and included in the study. Based on the patients’ documents, those with a history of ocular trauma or surgery and any corneal or other ophthalmic disorders were excluded from the study.
The Pentacam device uses a 475 nm monochromatic blue light-emitting diode (LED) with a 180-degree rotating Scheimpflug camera. The camera rotates around the optical axes of the eye and within 2 seconds captures a total of 25 images and produces a 3-dimensional model of the anterior segment of the eye. The instrument is capable of automatically analyzing the anterior segment, the anterior chamber, and the lens and performing the anterior and posterior topography of the cornea and pachymetry measurements.
Before performing the Pentacam imaging, patients were asked to stop using contact lenses for at least 2 weeks. The imaging was performed as follows. The patients were asked to place their chin on the chin rest of the device, press their forehead to the forehead strap, stare at a central target or fixation light, and, when a perfect alignment between the patients’ eye and visual axis was obtained, they were asked to blink, and then the imaging was performed. All measurements were based on the data from the annular ring that was 3 mm in diameter around the corneal apex. In our clinic, we routinely assess the Scheimpflug imaging parameters on the 3 mm corneal diameter. This would make our results comparable with the literature. The Pentacam images were reviewed, and those with a good quality were included in the study.
In patients with bilateral KC and in the normal group as well, only 1 eye of each participant was randomly selected. The randomization was performed using a series of random numbers generated by an independent statistician who were masked to the purpose of the study and diagnosis of the participants, using a computerized randomization program. The following parameters were recorded: anterior and posterior corneal astigmatism (ACA and PCA), astigmatism axis, central corneal thickness (CCT), and anterior and posterior mean keratometry (K). The severity of KC was classified according to the Amsler-Krumeich classification.
Anterior corneal astigmatism was classified as with-the-rule (WTR) when the steepest meridian of the corneal surface was between 60 and 120 degrees and as against-the-rule (ATR) when the steepest meridian was between 0 and 30 degrees or 150 and 180 degrees. Since the dioptric power of the posterior corneal surface is negative, posterior corneal astigmatism was classified as WTR when the steepest meridian was between 0 and 30 or 150 and 180 degrees and as ATR when the steepest meridian was between 60 and 120 degrees. The remaining values were classified as oblique astigmatism.
The power vector method was employed to quantify the relationship between astigmatism measurements. Conventional script notations of manifest refractions (sphere [S], cylinder [C], and axis [α]) were applied to calculate power vector coordinates. The method uses 3 fundamental vectors, including M = S + C/2, J 0 = (−C/2) cos2α, and J 45 = (−C/2) sin2α, where S is the sphere power, C is the cylinder power, α is the cylinder axis, and J is the Jackson astigmatic vector. M is the spherical lens equal to the spherical equivalent of the given refractive error. J 0 value is the cylinder power set at 90-degree and 180-degree meridians and J 45 value refers to a cross-cylinder set at 45 and 135 degrees. The overall blurring strength is calculated through the following formula: B = (M 2 + J 0 2 + J 45 2 ) 1/2 .
Receiver operating characteristic (ROC) curves were produced to determine the diagnostic significance of various astigmatism measurements. The area under ROC curves (AUROC) was calculated to describe the predictive accuracy of the different measurements and the optimized cutoff points that could best distinguish KC from normal eyes. An AUROC between 0.90 and 1.0 represents excellent discrimination, between 0.80 and 0.90 good, between 0.70 and 0.80 fair, between 0.60 and 0.70 poor, and between 0.50 and 0.60 very poor; <0.50 represents insufficient measures.
The best cutoff point was determined where the tests’ sensitivity and specificity were maximized. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated for the measurements with AUROC of ≥0.900 to assess the validity of cutoff points for predicting KC. The sensitivity (false negative) is defined as the ability of a test to correctly identify the patients with disease. The specificity (false positive) is defined as the ability of a test to correctly identify the patients without disease. PPV is the probability that patients with a positive screening test truly have the disease. NPV is the probability that patients with a negative screening test truly do not have the disease.
Statistical Analysis
Data analysis was performed using IBM SPSS Statistics (Version 22; IBM Inc, Armonk, New York, USA). The normality of the data was assessed using the Kolmogorov-Smirnov test, which revealed the data of anterior and posterior corneal astigmatism were not normally distributed. The results were demonstrated by mean ± standard deviation (SD). The χ 2 test was used to analyze categorical variables. The Mann-Whitney U test or Kruskal-Wallis test was used for the analysis of the continuous variables that were not normally distributed. The Spearman correlation test was used to evaluate the correlation between different variables. To evaluate the agreement between anterior and posterior astigmatism orientations, the Cohen kappa coefficient was applied. P value <.05 was considered statistically significant.
Results
This study included 1273 eyes of 1273 patients with keratoconus and 1035 eyes of 1035 control participants. The clinical characteristics and astigmatism measurements of the KC patients and the control group are demonstrated in Table 1 . The mean age of the KC patients was 25 ± 7 years and that of the control group was 25 ± 5 years. No significant difference was observed between the mean age and the sex of the KC and those of the control group ( P > .05). In the patients with KC, the mean magnitude of ACA and PCA was 4.49 ± 2.16 and 0.90 ± 0.43 diopter (D), respectively, which were significantly higher than that of the normal group ( P < .001).
Feature | Keratoconus (N = 1273) | Control (N = 1035) | P Value |
---|---|---|---|
Age (y) | 25 ± 7 | 25 ± 5 | .138 a |
Sex (male) | 739 (58.1%) | 580 (56.0%) | .176 b |
Mean K (D) | 50.2 ± 4.6 | 43.1 ± 1.15 | <.001 a ,∗ |
CCT (μm) | 450 ± 38 | 547 ± 32 | <.001 a ,∗ |
TCT (μm) | 431 ± 40 | 531 ± 33 | <.001 a ,∗ |
Astigmatism (D) | |||
ACA | 4.49 ± 2.16 | 0.93 ± 0.74 | <.001 a ,∗ |
PCA | 0.90 ± 0.43 | 0.26 ± 0.14 | <.001 a ,∗ |
ACA orientation | |||
WTR | 92 (7.2%) | 740 (71.5%) | <.001 b ,∗ |
ATR | 731 (57.4%) | 65 (6.3%) | |
Oblique | 450 (35.3%) | 230 (22.2%) | |
PCA orientation | |||
WTR | 805 (63.2%) | 10 (1.0%) | <.001 b ,∗ |
ATR | 94 (7.4%) | 925 (89.4%) | |
Oblique | 374 (29.4%) | 100 (9.7%) | |
M | −5.56 ± 4.2 | −2.69 ± 1.8 | <.001 a ,∗ |
Blur | 6.24 ± 4.00 | 2.80 ± 1.81 | <.001 a ,∗ |
The dominant astigmatism orientation of the anterior corneal surface was ATR in patients with KC and WTR in normal participants ( P < .001). The dominant astigmatism orientation of the posterior corneal surface was WTR in patients with KC and ATR in normal participants ( P < .001). In addition, spherical equivalent (M), J 0 , and J 45 were significantly higher in the patients with KC ( P < .001). The frequency distribution (percentages) of the anterior and posterior corneal astigmatism in the KC patients is shown in Figure 1 .
The mean magnitude of the anterior and posterior corneal astigmatism according to sex, age groups, and astigmatism orientation are shown in Table 2 . In KC patients, no significant differences were found between male and female subjects regarding ACA and PCA. In the normal group, male subjects had significantly higher PCA ( P < .001). In the KC patients PCA gradually decreased with increasing age, but the difference was not statistically significant ( P = .240). On the contrary, with increasing age PCA significantly increased in the normal participants ( P = .003). In the anterior corneal surface, the mean magnitude of ATR astigmatism was higher than WTR and oblique orientations in the KC patients ( P < .001). In contrast, WTR orientation of the anterior corneal surface had a higher magnitude in the normal group ( P < .001). Furthermore, in the posterior corneal surface, the mean magnitude of WTR astigmatism was significantly greater in the KC patients, and the mean magnitude of ATR astigmatism was significantly greater in the normal group ( P < .001). The distribution of the anterior and posterior corneal astigmatism of the KC patients in each age group is demonstrated in Figure 2 . Most eyes in all of the age groups showed ATR astigmatism in the anterior corneal surface, whereas WTR was the most prevalent astigmatism orientation of the posterior corneal surface.
Parameters | ACA (D) | PCA (D) | ||||
---|---|---|---|---|---|---|
Keratoconus | Normal | P Value | Keratoconus | Normal | P Value | |
Sex | ||||||
Male | 4.53 ± 2.29 | 1.00 ± 0.86 | <.001 a ,∗ | 0.89 ± 0.45 | 0.29 ± 0.15 | <.001 a ,∗ |
Female | 4.44 ± 1.97 | 0.84 ± 0.55 | <.001 a ,∗ | 0.91 ± 0.40 | 0.23 ± 0.11 | <.001 a ,∗ |
P value | .933 a | .328 a | ——— | .129 a | <.001 a ,∗ | ——— |
Age | ||||||
≤20 | 4.96 ± 2.41 | 0.95 ± 0.68 | <.001 a ,∗ | 0.95 ± 0.44 | 0.24 ± 0.11 | .001 a ,∗ |
21-25 | 4.52 ± 2.09 | 0.92 ± 0.73 | <.001 a ,∗ | 0.91 ± 0.43 | 0.25 ± 0.13 | <.001 a ,∗ |
26-30 | 4.07 ± 2.01 | 0.90 ± 0.64 | <.001 a ,∗ | 0.88 ± 0.42 | 0.28 ± 0.15 | <.001 a ,∗ |
31-35 | 4.46 ± 2.37 | 1.00 ± 1.05 | <.001 a ,∗ | 0.88 ± 0.46 | 0.27 ± 0.15 | <.001 a ,∗ |
≥36 | 4.44 ± 1.95 | 0.98 ± 0.83 | <.001 a ,∗ | 0.82 ± 0.44 | 0.29 ± 0.15 | <.001 a ,∗ |
P value | .002 b ,∗ | .946 b | ——— | .240 b | .003 b ,∗ | ——— |
Orientation | ||||||
WTR | 3.50 ± 2.02 | 1.07 ± 0.80 | <.001 a ,∗ | 0.95 ± 0.45 | 0.10 ± 0.04 | <.001 a ,∗ |
ATR | 4.83 ± 2.27 | 0.25 ± 0.20 | <.001 a ,∗ | 0.63 ± 0.38 | 0.27 ± 0.14 | <.001 a ,∗ |
Oblique | 4.15 ± 1.86 | 0.69 ± 0.46 | <.001 a ,∗ | 0.85 ± 0.37 | 0.22 ± 0.10 | <.001 a ,∗ |
P value | <.001 b ,∗ | <.001 b ,∗ | ——— | <.001 b ,∗ | <.001 b ,∗ | ——— |
Vector component | ||||||
J 0 | 1.05 ± 1.35 | -0.25 ± 0.35 | <.001 a ,∗ | 1.21 ± 1.33 | -0.34 ± 0.45 | <.001 a ,∗ |
J 45 | 0.02 ± 1.76 | −0.11 ± 0.48 | .017 a ,∗ | −0.11 ± 1.67 | 0.19 ± 0.27 | <.001 a ,∗ |
The axis orientation of anterior and posterior corneal surfaces according to each other is presented in Table 3 . ACA and PCA had the same axis orientation in 324 eyes (25.4%), in which 20 (of the total 1273) eyes (1.6%) had WTR, 17 eyes (1.3%) had ATR, and 287 eyes (22.5%) had oblique orientation in both anterior and posterior surfaces. Moreover, there was a significant agreement between the axis orientations of ACA and PCA in the KC patients (ĸ = 0.077, P < .001). On the other hand, no significant agreement was found between the axis orientations of the ACA and PCA in the normal group (ĸ = 0.003, P = .626). Figure 3 shows the correlation scattergram between the magnitudes of the anterior and posterior corneal astigmatism in the patients with KC. The Spearman correlation analysis revealed that ACA had a significant positive correlation with PCA in the patients with KC (r = 0.785, P < .001) and the normal participants (r = 0.486, P < .001).
PCA Orientation | Total | |||
---|---|---|---|---|
WTR | ATR | Oblique | ||
ACA orientation | ||||
WTR | 20 {1.6%} (21.7%) [2.5%] | 51 {4.0%} (55.4%) [54.3%] | 21 {1.6%} (22.8%) [5.6%] | 92 {7.2%} (100%) [7.2%] |
ATR | 648 {50.9%} (88.6%) [80.5%] | 17 {1.3%} (2.3%) [18.1%] | 66 {5.2%} (9.0%) [17.6%] | 731 {57.4%} (100%) [57.4%] |
Oblique | 137 {10.8%} (30.4%) [17.0%] | 26 {2.0%} (5.8%) [27.7%] | 287 {22.5%} (63.8%) [76.7%] | 450 {35.3%} (100%) [35.3%] |
Total | 805 {63.2%} (63.2%) [100%] | 94 {7.4%} (7.4%) [100%] | 374 {29.4%} (29.4%) [100%] | 1273 {100%} (100%) [100%] |