The onset of keratoconus is at puberty. It is a slowly progressive disorder in which the cornea assumes an irregular conical shape as a result of central or paracentral noninflammatory thinning of the cornea. The corneal thinning induces irregular astigmatism, myopia, and protrusion, causing mild to marked impairment in the quality of vision. Keratoconus is generally a bilateral, corneal ectatic, enantiomorphic disease; however, the clinical severity of involvement is often asymmetrical. Signs and symptoms are highly variable and primarily depend on the severity of the disease and location of the cone apex.1 Spectacles and contact lenses are the main treatment methods for mild and moderately affected eyes. Implantation of intracorneal ring segments (Intacs) may be an alternative management method for contact-lens-intolerant patients.2–4 Also, some refractive surgeons advocate photorefractive keratectomy to reduce the steepness of the cone.5 There are also successful reports of stabilizing keratoconic corneas by collagen crosslinking of the photosensitizer riboflavin and ultraviolet A light.6 Corneal grafting is the only surgical alternative in cases of advanced keratoconus.
Accurate measurement of anterior segment parameters, especially corneal thickness and anterior chamber depth (ACD), is crucial for preoperative assessment, planning, and follow-up of all surgical methods of managing keratoconus. Several studies7–9 have compared anterior chamber parameters in healthy eyes using different instruments. However, data on anterior chamber parameters in keratoconic eyes with the progression of the disease are limited. We designed this study to document the alterations in anterior chamber parameters with the progression of keratoconus.
PATIENTS AND METHODS
Two hundred sixteen eyes of 123 patients diagnosed with keratoconus and 224 eyes of 112 age-matched control subjects with simple refractive errors were studied using the Pentacam Comprehensive Eye Scanner (CES). Pentacam software data for each examination were used for retrospective evaluation.
An eye was diagnosed as having keratoconus if there were a scissoring reflex on retinoscopy and central or paracentral steepening of the cornea on topography with at least 1 of the following clinical slitlamp findings: stromal thinning, anterior bulging, or conicity, Vogt striae, Fleischer ring, Descemet's breaks, apical scars, and subepithelial fibrosis. According to mean keratometry (K) readings obtained from the topographic map of the Pentacam, keratoconus eyes were divided into 3 groups—mild (K = less than 47.0 diopters [D]), moderate (K = 47.0 to 52.0 D), and severe (K = 52.0 D or higher)—as described in the literature.10,11 Patients who had worn a contact lens within the past 6 months, eyes with ocular surgical anamnesis, and eyes with other pathology or serious scarring were excluded from the study. The control group was enrolled from patients with refractive errors of less than ±3.0 D sphere and 1.0 D cylinder without other ocular pathology.
For the Pentacam measurements, patients sat on a chair. The chin was placed on the chinrest, and the forehead was pressed against the forehead strap in dim-light conditions. Patients were asked to look with both eyes open into the black spot in the middle of the instrument's blue fixation beam. At the same time, the researcher observed the image of the eye on the monitor, brought the image into focus, and centered it within the aiming circle with the help of markings on the monitor. When a clear image was maintained and focused, the instrument took the Scheimpflug images automatically.
The Pentacam CES system is based on a 180-degree rotating Scheimpflug camera that can take 12 to 50 single captures to reconstruct the anterior chamber. In this study, anterior segment reconstructions were produced with 25 single captures. After completing a scan, the Pentacam software constructs the 3-dimensional image of the anterior segment and calculates the anterior chamber parameters, allowing measurement of the thinnest corneal thickness (TCT), ACD, corneal volume (CV), anterior chamber angle (ACA), and anterior chamber volume (ACV).
Statistical analyses were performed with SPSS for Windows (version 12.0, SPPS, Inc.). All data were reported as means ± standard deviation. Normality for continuous variables in the groups was determined by the Shapiro-Wilk test. The variables showed normal distribution (P>.05). One-way analysis of variance was used to compare variables within groups. The Bonferroni correction test was used for dual comparison. Categorical variables were analyzed with the chi-square test. The Pearson correlation test was used to evaluate the correlation of parameters. For each parameter, the following were calculated: area under the operation characteristic curve (ROC); standard error of the ROC; cutoff values for parameters; and sensitivity, specificity, and accuracy level of the cutoff values. A value of P<.05 was considered statistically significant.
Binocular keratoconus was diagnosed in 93 patients and monocular keratoconus in 30 patients. Most fellow eyes in cases of monocular keratoconus were in patients who were excluded because of corneal scarring or previous ocular surgery (penetrating keratoplasty [PKP], Intacs implantation) or because the severity of the keratoconus did not allow Pentacam measurements.
One hundred twenty-nine eyes had mild keratoconus, 59 had moderate keratoconus, and 35 had severe keratoconus. The mean age of the 53 women and 70 men in the keratoconus group was 27.3 ± 9.1 years (range 12 to 63 years). The mean age of the 55 women and 57 men in the control group was 28.5 ± 8.8 years (range 13 to 64 years). Table 1 shows the patients' demographics. There were no statistically significant differences between the keratoconus group and control group in age, sex, or eye distribution (P>.05).
Table 2 shows the mean TCT, ACD, ACA, CV, and ACV values. The ACA and CV were statistically significantly different between the mild keratoconus and severe keratoconus groups. However, the ACA and CV were not statistically significantly different between the moderate keratoconus group and the other keratoconus groups. The CV measurements in the control group were statistically significantly different from those in all keratoconus groups (P<.05); however, there was no difference in ACA (P>.05).
Progressive thinning of the cornea is a well-known feature of the pathophysiology of keratoconus.12 Corneal thickness measurements of keratoconic corneas have been studied with various instruments.8,13,14 Also, many studies7,15–17 have compared the reproducibility and reliability of instruments with different operating principles. Ultrasound (US) pachymetry remains the gold standard for corneal thickness measurement. However, the need for topical anesthesia, risk for infection, necessity of alignment exactly at the center of the cornea, and proper handling of the probe perpendicular to the corneal surface are major drawbacks of the technique. The limitations of the US pachymeter led to the development of less invasive techniques that are reliable, repeatable, and operator independent. These include the Pentacam, Orbscan, optical coherence tomography, and optical low-coherence reflectometry. In 2006, Uçakhan et al.13 compared the Pentacam system, noncontact specular microscopy, and US pachymetry in normal and keratoconus patients. The central corneal thickness (CCT) readings were statistically different with each technique. Their TCT measurements with the Pentacam were close to our measurements, especially in the mild keratoconus group (478.6 μm versus 484.8 μm). In our study, the TCT measurements progressively decreased with the progression of the disease. Progressive corneal thinning is a well-known indicator of the progression of keratoconus.
The Pentacam system can evaluate the cornea and anterior segment of the eye from the anterior surface of the cornea to the posterior surface of the lens. Anterior chamber depth is a major parameter of the Pentacam. In our study, the mean ACD in all keratoconic eyes was 3.3 ± 0.3 mm, higher than the mean (3.1 ± 0.3 mm) in the control group. Even in mild cases, the ACD was significantly deeper than in the control group and the ACD became deeper as the disease progressed. The mean ACD in our control group was lower than the values reported by Rabsilber et al.18 In their study, the mean ACD was 2.9 ± 0.3 mm in a group of 76 healthy volunteers with a mean age of 46.6 ± 16.8 years. The difference in ACD in these groups may be related to age; our control group comprised younger subjects. In our study, the difference in mean ACD between the severe and mild keratoconic groups was 0.46 mm, an almost 14% increase in depth with the progression of the disease. This increase in ACD was larger than the change in TCT. Thus, anterior protrusion of the central corneal may be a source of the increase. Accurate measurement of the ACD is of paramount importance in the implantation of phakic intraocular lenses (pIOLs), and there are reports of pIOL implantation for the management of keratoconus.19,20 Thus, the progressive increase in ACD may be an advantage in keratoconic patients in terms of implantation of pIOLs.
In 2006, Ambrosió et al.21 reported that the CV measurements in eyes with mild to moderate keratoconus were significantly lower than those in a group of normal eyes. According to the authors, keratoconic corneas had a mean volume 0.94 mm3 less than the mean volume in normal eyes. Similar to this report, our results showed a progressive decrease in CV with the progression of the disease. In our study, the mean CV in the severe keratoconus group was 2.30 mm3 smaller than that in the mild keratoconus group. Also, the severe group had statistically significantly lower CV readings than the control and mild keratoconus groups (P<.05). The mean CV measurements analyses were significantly different between all keratoconus groups compared with those in the control group (P<.05). However, the mean CV measurements analyses were not significantly different within the keratoconus groups.
Implantation of Intacs is an alternative surgical modality for patients with clear corneas who are not satisfied with contact lenses or spectacles. Surgeons have tried to implant the ring segments to 70% depth of the cornea within a 7.0 mm optical zone. Even with procedures performed by the most experienced surgeons, there are reports of ring-segment extrusion.4 Previously, corneal thickness was the only major parameter to consider before implantation of ring segments. However, we believe that if surgeons focus on the CV within the 7.0 mm optical zone, the risk for extrusion may be reduced.
The mean ACA was 36.2 degrees in the keratoconus groups at the end of analysis. However, detailed investigation showed that as the keratoconus became more severe, the peripheral cornea of the eye became flatter and the ACA smaller. The mean ACA was 37.2 degrees in the mild keratoconus group, 35.6 degrees in the moderate group, and 33.6 degrees in the severe group. This represents an almost 10% decrease in the ACA as the disease progressed. This peripheral flattening may be important for incisions in intraocular surgery. Spherical or toric pIOL implantation, PKP, and, more frequently, cataract surgery are commonly performed in keratoconic eyes; during preparation of incisions, surgeons should keep in mind that the posterior corneal surface in severely affected keratoconic eyes is closer to the iridolenticular surface than it is in eyes with mild keratoconus. Our findings support those of Smolek and Klyce,22 who found that to compensate for the increase in central curvature in the region of the cone, the peripheral cornea becomes flatter and that as the disease progresses, this may result in lower ACA measurements. In contrast, the mean ACA in the control group was 36.89 degrees, lower than in the eyes with mild keratoconus and higher than in the eyes with moderate to severe keratoconus.
Despite the presence of a statistically significant increase in ACD, the progressive increase in the ACV did not reach statistical significance. The ubiquitous increase in ACD and ACV may provide an extra potential space in the management and treatment alternatives. Our ACV measurements were clearly higher in all groups, even in the mild group, than those of Rabsilber et al.18
We also performed a correlation analysis of the 5 study parameters with the mean K-readings in the keratoconus groups (Table 3). There was a statistically significant correlation between all parameters and the mean K-readings; the correlation was negative for TCT, CV, and ACA and positive for ACD and ACV. A high K-reading with a thin central cornea is a typical finding in keratoconus. Probably, the progressive thinning that occurs with keratoconus leads to a progressive decrease in CV. Also, with the progression of the disease, central cone protrusion is compensated for by peripheral corneal flattening and a decrease in ACA. On the other hand, central cone protrusion is also associated with a deeper anterior chamber at the center. The increase in ACD may be the source of the increase in ACV.
The ROC analysis for each parameter showed that the area under the curve (AUC) was acceptable only for the horizontal, vertical, and mean K-readings. Table 4 shows the AUC values, standard error of the ROC, cutoff values for these parameters, and the sensitivity, specificity, and accuracy level of the cutoff values. According to data we obtained from a study group composed of control and keratoconus subjects, a vertical K-reading of 45.05 D seems to be a reliable cutoff value, with reasonably high sensitivity, specificity, and accuracy.
Identification of the subclinical forms of the keratoconus in patients with few or no clinical signs is challenging. Identifying very early forms of keratoconus or forme fruste keratoconus is important for evaluating and following patients considered to have asymmetrical or unilateral keratoconus. The data presented in our study are from patients with clinically easily diagnosed keratoconus with obvious clinical features, as stated previously. As our study did not have a meaningful number of patients, we could not present the data on subclinical keratoconus patients. Thus, a study of the anterior chamber parameters in a group of patients with forme fruste keratoconus may provide useful data for a better understanding of keratoconus. Meanwhile, a recent study clearly documented the high sensitivity and specificity of higher-order aberrations in the detection of subclinical forms of keratoconus.23
The Pentacam is an easy-to-use anterior segment analysis system, and its high reliability and repeatability independent of the operator have been clearly documented by Barkana et al.7 In that study, the mean coefficient of repeatability for central thickness measurements was higher with the Pentacam system than with a US pachymeter. Also, the interoperator reproducibility of the Pentacam was excellent. The difference in mean CCT measurements taken with 2 operators was almost 1 μm, which means highly accurate measurements independent of the operator.
In conclusion, based on the data in our study, we think the effect of keratoconus is not limited to corneal thickness. Rather, it affects all anterior segment parameters of the eye and results in significant alterations with the progression of the disease. To more clearly understand these alterations, a large series with long-term follow-up is mandatory.
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