Keratoconus Asymmetry between Both Eyes Based on Corneal Tomography.

PURPOSE: To characterize the asymmetry between both eyes in patients with keratoconus based on corneal tomography.
MATERIALS AND METHODS: All patients with keratoconus who presented to the eye clinic at Jordan University Hospital between January 2008 and November 2011 were included in the study. Using computerized corneal tomography, the keratometric values and indices of both eyes of participants with keratoconus and normal controls were compared. For both eyes to be considered symmetrical, the difference between the mean curvature power (Km), flat curvature power (K1), or steep curvature power (K2) in both eyes was equal to or <2.5 diopters, and the difference between the thinnest corneal points was equal to or <25.0 μm between both eyes.
RESULTS: Ninety-eight patients with keratoconus and 49 normal participants were evaluated. The mean age of the participants was 26.3 ± 6.6 years. The results showed two populations of patients with keratoconus: one with asymmetrical corneas who were more affected by the disease and another with symmetrical corneas. As the disease severity increased, the differences between the two eyes increased for patients with the asymmetrical form, while both corneas of patients with the symmetrical form were similar.
CONCLUSIONS: Corneal tomography identified two forms of keratoconus: symmetrical and asymmetrical. The latter tended to be more severe and occurred in a younger age group. Questions remain about whether the two keratoconic forms are specific to the Middle Eastern population and whether there are ethnic or demographic forms of the disease.

Introduction

Keratoconus is a noninflammatory disorder, the first signs of which generally appear during the second decade of life.[1] The disease is characterized by a progressive change in the corneal curvature leading to thinning and anterior protrusion of the corneal surface.[2] This morphologic corneal transformation causes distortion of the image reaching the retina that is correctable initially with optical solutions but with disease progression requires surgical intervention.[3] As with other progressive diseases, the management of keratoconus depends largely on its evolutionary characteristics.[4]

The etiology of keratoconus remains unclear. Both intrinsic (genetic) and external (allergies and eye rubbing) factors play a role, yet the contribution of each factor to the disease remains unclear.[5678] A popular hypothesis suggested that keratoconus develops in individuals with a genetic predisposition where an environmental factor is present to trigger its onset.[9] Nevertheless, a higher disease prevalence has been found among specific ethnic groups, for example, Asians compared to white Caucasians in the UK,[5] Maori compared to Europeans in New Zealand,[10] or groups of families in northern Finland.[5] The morphologic changes observed at the cellular level point toward heterogeneity in the pathophysiological characteristics of the disease.[11]

Recently, Choi and Kim[12] found that over a 1-year period, 25% of keratoconic eyes progressed faster than the rest of the sample, suggesting the presence of at least two forms of the disease.[12] Since the management of keratoconus depends largely on the disease characteristics and knowledge of the existing subtypes and eyes with keratoconus have a greater degree of interocular asymmetry than normal eyes,[1314] the current study attempted to characterize the different keratoconic forms and the difference between both eyes using computerized corneal tomography of patients with keratoconus with different disease stages.

Materials and Methods

We retrospectively reviewed the charts of 98 patients with keratoconus and 49 normal participants without keratoconus who presented to the eye clinic at Jordan University Hospital for the first time between January 2008 and November 2011. The Local Institutional Review Board and Ethics Committee of Jordan University Hospital and The Faculty of Medicine approved the study protocol, which adhered to the tenets of the Declaration of Helsinki. All patients (mean age of the participants was 26.3 ± 6.6 years [range, 13-48 years]) underwent a complete ophthalmic examination that included measurements of the corrected and uncorrected visual acuity levels, slit-lamp examination, retinoscopy, fundus evaluation, and corneal tomography (Pentacam HR rotating Scheimpflug camera, Oculus, Optikgerate GmbH, Wetzlar, Germany). Patients were diagnosed with keratoconus based on the following criteria: scissoring of the retinoscopic reflex with hard neutralization during retinoscopy, stromal thinning, apical decentration and conical protrusion, and the presence of Fleischer's ring and Vogt's striae.[411] In addition to the patients with keratoconus, keratometric measurements and indices of the eyes of 49 persons (mean age, 28.5 ± 6.9 years) without signs of keratoconus were studied using the same Pentacam tomographer. All participants either did not wear contact lenses or had removed the lenses at least 3 weeks before the measurements. No patients or normal participants had undergone a previous ocular surgery or sustained a previous ocular trauma.

Measurements were obtained from color printouts produced by the Pentacam HR software. For a pair of eyes to be considered symmetrical, the difference between the mean curvature power (Km), flat curvature power (K1), or steep curvature power (K2) in both eyes had to be equal to or <2.5 diopters (D), and the difference between the thinnest corneal points had to be equal to or <25.0 μm between both eyes. These criteria were based on values obtained in normal participants.[1315] The laterality of the corneas was not considered during the analysis, and the differences between eyes are expressed in absolute values.

Statistical analysis was performed using the IBM SPSS Statistics version 20.0 (IBM Corporation, Somers, New York, USA). Participants' characteristics were investigated by calculating the frequencies, percentages, and means and standard deviations. The following statistical analyses were performed: Kolmogorov–Smirnov test to evaluate the normality of study variables; Levene's test to study the homogeneity of variances; Kruskal–Wallis nonparametric test to explore differences among normal, symmetrical, and asymmetrical eyes; and post hoc tests (Mann–Whitney) with a Bonferroni correction (P < 0.0167) to allocate differences between the study groups while controlling for age as a covariant.

Results

Ninety-eight patients with keratoconus were included (27 cases were considered symmetrical and 71 asymmetrical) and compared to 49 normal participants. The mean age of the participants was 26.3 ± 6.6 years (range, 13–48 years; median age, 23 years). About 50.3% were males [Table 1].

Table 1

Demographic characteristics of the study groups

Table 2 shows the differences between both eyes measured by computerized corneal tomography (highest value–lowest value) in keratoconic patients and normal participants.

Table 2

Comparison of the differences in absolute values between both eyes in the three groups

Despite the small interocular differences among the normal group, there were no cases in which the eyes were identical mirror images of each other in which all differences are zero. When comparing the interocular values between the symmetrical and asymmetrical keratoconic groups and normal participants for the 10 parameters studied, significant (P < 0.05) differences were found among the three groups in the mean Km, K1, and K2 curvature powers, corneal asphericity coefficient, apex thickness, thinnest corneal location, and basement membrane density. The differences were particularly large when comparing the flat and steep curvature powers and the apex and thinnest thicknesses. The corneal volume and anterior chamber depth differed significantly between the two keratoconus groups and between the asymmetrical group and the normal group but not between the symmetrical group and the corneas of the normal participants. The differences in anterior chamber volume were not significant for any of the groups compared [Table 2], while Table 3 shows the mean keratometric values of each group.

Table 3

Comparison of the mean keratometric values between the three groups

The Km for the worst eye differed significantly for all three groups, with the asymmetrical group of keratoconus participants the most affected. When both eyes were considered (for the other eight keratometric parameters), only the basement membrane density and the anterior chamber depth differed significantly among the three groups. However, the normal eyes differed significantly from the keratoconic eyes (symmetrical and asymmetrical) in all other parameters studied except for the anterior chamber volume, which was only significant in the asymmetrical versus normal groups [Table 3].

Although similar in means and ranges, statistical analysis showed that participants' ages differed significantly between the two keratoconus groups and between the asymmetrical and normal groups. However, age was only poorly correlated with the interocular differences in Km (normal group, R2 = 0.0015; keratoconus group, R2 = 0.0034) and the thinnest point (normal group, R2 = 0.0135; keratoconus group, R2 = 0.0061) [Figures 1–3].

Figure 1

Comparisons between the Km values in the worst eye and the interocular differences for the asymmetrical group. For each patient, the Km of the worst eye was plotted against the interocular difference in Km

Figure 3

Comparisons between the Km values in the worst eye and the interocular differences for the normal group. For each patient, the Km of the worst eye was plotted against the interocular difference in Km

The interocular difference in Km had a higher correlation with the Km in the worst eye of the asymmetrical group (R2 = 0.5741) [Figure 1] than in the symmetrical group of patients with keratoconus (R2 =0.0456) [Figure 2] or the normal participants (R2 = 0.0147) [Figure 3]. As the power of the Km increased, the difference in the Km between both eyes increased, mainly in the asymmetrical group [Figure 1].

Figure 2

Comparisons between the Km values in the worst eye and the interocular differences for the symmetrical group. For each patient, the Km of the worst eye was plotted against the interocular difference in Km

Discussion

Keratoconus is a chronic progressive ectatic disorder of the cornea for which treatments differ based on the severity of the corneal changes.[41617] Early detection of keratoconus in the preclinical stage is important for preventing ectasia after laser in situ keratomileusis.[1819] The mean age of our keratoconic patient was about 25 years, which was similar to that in the study of Bae et al.[18]

The current results suggested that there are two distinct forms of keratoconus based on interocularity, i.e., the symmetrical form, representing 28% of our sample, and the asymmetrical form that affected most of the patients with keratoconus. Symmetrical keratoconus was characterized by small interocular differences in the corneal curvature power and the thicknesses between both eyes. The population with the asymmetrical form was younger and was more severely affected by the disease than those with the symmetrical form, and the interocular difference in Km was correlated highly with disease severity, which was not the case in the symmetrical group [Figure 1].

Since the early years of keratometry, the general consensus remains that keratoconus is an asymmetrical condition.[20] Burns et al.[13] reported interocular corneal asymmetry and Nichols et al.[21] found that the asymmetry increased with disease progression. More recently, Bae et al.,[18] Henriquez et al.,[22] and Ruiseñor Vázquez et al.[23] compared the interocular symmetry between participants with normal corneas and a group of keratoconic patients and found significant differences between the keratoconus and normal groups in almost all measured parameters when comparing unilateral keratoconus with its fellow eye or with a normal control group, which was also the case in the current series [Table 2]. Similar to the current series, Uçakhan et al.[24] also found that the corneal power and elevation measurements were significantly (P < 0.05 for all comparisons) higher, and the cornea was significantly thinner in eyes with subclinical or clinical keratoconus than in normal eyes and that combined analysis of the anterior and posterior corneal powers, elevation, and thickness data provided by the Scheimpflug device discriminated between ectatic corneas and normal corneas.[24] Du et al.[25] recently found that as keratoconus progresses, different indices (anterior versus posterior curvature indices) become more significant on Pentacam tomography when keratoconus becomes severe.[25] In the current study, the interocular differences were smaller in normal participants than in the patients with keratoconus. Similar to Lema et al.,[26] the mean keratometric values for the normal group in the current series was 43.27 ± 1.26 D compared to 43.58 ± 1.71 D in their study. The keratoconus group in their study had a mean of 51.45 ± 6.65 D compared to 53.09 ± 6.14 and 48.87 ± 4.27, respectively, for the asymmetrical and symmetrical groups in the current study [Table 3]. Emre et al.[27] showed that the corneal volume measurements in the control group differed significantly from those in the keratoconus group. Similar to the current series, we found that the corneal volume differed significantly between the normal group and both symmetrical and asymmetrical keratoconus groups [Table 3].

There were more patients in the asymmetrical group than in the symmetrical group in a ratio of 3:1, and the interocular differences of the asymmetrical groups were larger by a factor of 5–3. The pooling of data inevitably resulted in averages close to the values of the asymmetrical group. In fact, the amplitudes of the interocular differences obtained by other research groups are in the same ranges as those of the current symmetrical and asymmetrical groups.[13212228] The results of the Collaborative Longitudinal Evaluation of Keratoconus study,[29] which concluded that patients with severe keratoconus also have more asymmetrical disease, were valid for the current asymmetrical group, which included most of the patients and thereby outweighed the symmetrical group when the data were pooled.

The interocular asymmetry of the keratoconic corneas was reported earlier at the morphologic level of the corneal map.[1020] Although relatively small (on average 1 D for the corneal power and 10 μm for the thickness as shown in Table 2), the interocular differences in the symmetrical group were significantly larger than those of the participants with normal eyes. In the current study, the differences obtained in normal participants were in the same range as those in other studies.[1518] In the symmetrical group, the disease severity was not correlated with the interocular differences, suggesting that in this population, the shapes of both corneas change symmetrically with disease progression [Figure 1]. There were, nevertheless, significant differences between the symmetrical group and the normal participants, which supported the hypothesis of Myrowitz et al. that interocular asymmetry can be used to predict corneal abnormalities,[30] and an interocular difference outside the normal range should alert the physician to examine for other parameters to detect subclinical keratoconus.[15]

Although a small part of the interocular difference may be attributed to the intercessional variability, a large degree of asymmetry outside the normal range of interocular differences should prompt clinicians to repeat examinations and search for other parameters and warrants more extensive evaluation, which may help in predicting and avoiding postoperative ectasia.[153031]

The questions as to whether the two forms of keratoconus described in this report are specific to the Middle Eastern population and whether or not there are ethnic or demographic forms of the disease remain unanswered. Since the clinical management of keratoconus depends largely on the characteristics of its progression, knowledge on the existing subtypes is essential for providing optimal management.

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Conflicts of interest

There are no conflicts of interest.