Purpose
To evaluate the prevalence of keratoconus (KC) and other corneal abnormalities by means of videokeratography and tomography in a large series of patients affected by vernal keratoconjunctivitis (VKC).
Design
Cross-sectional study.
Methods
Setting : Single-center children’s hospital. Study Population : A total of 651 consecutive patients with VKC and a control group of 500 were prospectively recruited between May 1, 2012 and September 30, 2013, with a minimum follow-up of 12 months. Observation Procedure : All patients were evaluated by means of a Scheimpflug camera combined with a Placido corneal topographer. Keratoconus, suspected keratoconus, or its absence were determined in each patient. The corneal symmetry index of front (SI f ) and back curvature (SI b ), shape indices, and thicknesses were compared between the 2 groups. Main Outcome Measures : Prevalence of keratoconus and corneal indices modifications.
Results
Five out of 651 patients (0.77%) demonstrated topographic signs of KC. Two of them were bilateral. All patients were older than 7 years of age, and the mean age was 11.54 years. Four other patients (0.61%) were classified as KC suspects by the screening program. Of 304 patients older than 11 years (mean age 14.4 years), 4 (1.32%) were found to have KCN, and 4 (1.32%) were KC suspects. The corneal indices of patients in the VKC group were extremely similar to those in the control group. ( P > .05).
Conclusions
The prevalence of KC in our patient population, compared with previous reports in the literature, is much lower. The similar corneal indices in both groups suggest the absence of permanent corneal deformation due to VKC.
Vernal keratoconjunctivitis (VKC) presents as a severe chronic bilateral inflammation of the ocular surface characterized by seasonal exacerbations that occurs predominantly in children and young adults. VKC is typically characterized by the presence of giant “cobblestone” papillae in the upper palpebral conjunctiva (tarsal form) or at the limbus (bulbar form), and corneal involvement is often present, ranging from superficial keratitis to shield ulcers. Patients complain of itching, burning, and severe photophobia. The etiology of VKC is still unknown, but a Th2-driven response seems to be the main mechanism involved in the pathogenesis of the disease. Th2 lymphocytes are responsible for hyper-production of IL-4 and IL-5 with consequent activation of mast cells and eosinophils. Increased levels of matrix metalloproteinases MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-10 have been found in VKC patients. The long-term prognosis is generally good; however, 6% develop sequelae responsible for permanent visual impairment.
Since 1983, several studies have reported an association between VKC and keratoconus (KC). Keratoconus is a bilateral, noninflammatory ectasia of the cornea that is characterized by progressive stromal thinning, and it has been found to occur at a rate of approximately 1 in 2000 in the general population. The etiology of this disease is unclear, as both genetic and environmental factors seem to play an important role in its pathogenesis. Recent studies suggest that eye rubbing and chronic mechanical trauma of the corneal epithelium inducing keratocyte and fibroblast apoptosis mediated by cytokines could cause the evolution of keratoconus. In a mouse model of atopic dermatitis and blepharitis, Ebihara and associates found a correlation between eye rubbing and cone shaped deformity of the cornea.
The diagnosis of KC has been initially based on clinical signs visible with a slit lamp, such as central or inferior thinning and protrusion of the cornea, Vogt striae in the posterior stroma, scars in the Bowman layer, and a Fleischer ring. Unfortunately, these signs become evident only in advanced stages of the disease. With the advent of computer-assisted topographic analysis, the evaluation of different corneal indices has provided more precise diagnosis of clinical and suspected keratoconus. Recently, corneal topographers have achieved the ability to diagnose KC even earlier by analyzing the front corneal surface first, and then measuring both the anterior and posterior surfaces of the cornea.
In 2001 Totan and associates used a topographic approach to demonstrate the correlation between VKC and KC. To detect keratoconus with Placido disc–based videokeratography, the corneal topographic data were quantitatively analyzed by means of the modified Rabinowitz-McDonnell test. The authors found that 26.8% of a sample of 82 patients with VKC (mean age 15.7 years) also had KC. Dantas and associates found that in a younger group of patients with VKC (mean age 10.6 years), 22.5% of patients demonstrated topographic changes consistent with KC according to Holladay Diagnostic Summary compared to 9.5% showing clinical signs diagnosed with a slit lamp. Furthermore, in a group of 40 patients with VKC (mean age 10.1 years), Lapid-Gortzak and associates found that 11.25% demonstrated clinical findings and 16.25% demonstrated topographic findings consistent with keratoconus. Barreto and associates in 2007 refined the diagnostic methods of evaluating for KC by analyzing both the anterior and posterior corneal morphology of 50 patients using combined slit scanning and the Placido topography in a group of patients with VKC (mean age 16.4 years) and an age-matched control group. They found that 20% of eyes had keratoconus and 14% had subclinical keratoconus.
In our hospital, we have a very large population of children with VKC, and it was our impression that very few of these patients had KC. The purpose of our study was to determine the prevalence of KC in a large group of patients affected by VKC compared with controls. In addition, we sought to evaluate if the corneal indices as measured by topography differed among the 2 groups.
Methods
This prevalence study was approved by the Ethical Committee of A. Meyer Children’s Hospital. All patients visiting the Pediatric Ophthalmology Unit and the Allergy and Clinical Immunology Unit of A. Meyer Children’s Hospital (Florence, Italy) between May 1, 2012 and September 30, 2013 and who had VKC were enrolled. Per the usual practice regimen of the ophthalmologists, all patients with VKC were treated with topical cyclosporin A eye drops 1.2% in saline or 2% in olive oil 2–4 times daily depending on the severity of the disease. Patients who did not meet the minimum follow-up of 12 months were excluded from the study. Patients with a previous history of ocular surgery or anterior segment diseases (other than VKC), those who wore contact lenses, or those who were not able to cooperate with the ophthalmic examination were also excluded from the study. Patients with VKC and a corneal shield ulcer were also excluded, as scarring would have altered the topographic indexes. Severity of VKC was classified on the basis of subjective and objective signs using a previously reported scoring system.
To compare the corneal morphology of VKC patients with those of a normal population, we enrolled 500 patients presenting to the ophthalmology clinic of our institution who did not have anterior segment or allergic eye diseases or previous ocular surgery, and who had at least 20/20 best-corrected visual acuity, to serve as the control group.
All patients who fulfilled the inclusion criteria underwent a complete ophthalmologic examination, including visual acuity measurement, cycloplegic refraction, slit-lamp examination, fundus examination, and corneal topography and tomography. Corneal morphology features, such as corneal thickness, anterior and posterior corneal curvature, and elevation, were evaluated by means of a Scheimpflug camera combined with Placido corneal topographer (Sirius, software version 2.6; CSO, Florence, Italy). The device’s scanning process produces 1 keratoscopy image and a series of 25 Scheimpflug images. Anterior data were derived from Scheimpflug images and Placido information jointly. All other measurements for internal structures (posterior corneal surface, anterior lens surface, and iris) were derived solely from Scheimpflug data. Previous studies have reported that the system’s pachymetric and shape measurements (curvature, eccentricity, elevation) have good accuracy and repeatability.
According to the manufacturer’s guidelines, a single experienced examiner performed all corneal measurements. One scan per eye was obtained for each patient. Every examination was critically reviewed for quality of topographic and tomographic images, alignment, and measurement coverage; in the case of poor quality (eg, from excessive movement or from poor-quality tear film), a new scan was repeated, and in case of further failure, the patient was excluded from the study. To compare the morphology between the VKC and control group, we elected to analyze only the right eyes to remove the intercorrelation between fellow eyes: although axis-symmetric indices were selected, the following considerations could be extended for enantiomorphism also to the left eye.
The following indices were evaluated to compare the VKC and control groups.
Symmetry Index of Front and Back Corneal Curvature
The symmetry indices of the front (SI f ) and back corneal curvature (SI b ) are defined as the difference in anterior and posterior tangential corneal curvature, between 2 circular zones centered on the vertical axis in the inferior and superior hemispheres (center: x = 0 mm; y = ±1.5 mm, radius: 1.5 mm). Positive values indicate a steeper inferior hemisphere, whereas negative values indicate a steeper superior hemisphere.
Shape Indices
Anterior shape indices are based on the approximation of the front surface of the cornea to an aspherotoric reference shape. The aspherotoric surface is defined as
where R(ρ,θ)=rff−(rff−rsf)sin(θ−Axf)2
R ( ρ , θ ) = r f f − ( r f f − r s f ) sin ( θ − A x f ) 2
and are the polar coordinates of a given point.
The following indices are the parameters that define the reference within a chosen diameter:
- •
Rf=rff+rfs2
R f = r f f + r f s 2
is the average curvature of the reference, where rf f and rs s are its principal meridians expressed in mm;
- •
the orientation ( Ax f ) of the flattest meridian of the reference expressed in degrees;
- •
the asphericity ( p f ) of the reference (expressed as p = 1 + Q ).
Because just normal corneas show regular surfaces, the root mean square (RMS f ) of the deviation between the anterior surface and its reference is a measure of asymmetry and irregularity. A more comprehensive index can be defined as the ratio between RMS f and the fitting area (RMS/A f ) expressed in μm/mm 2 . Similarly, rf b , rs b , R b , Ax b , p b , and RMS/A b are defined for the posterior surface of the cornea. For our study, the default value of the diameter was chosen for the analysis (Ø = 4.5 mm).
Thickness-Based Indices
An index based on the thinnest value of corneal pachymetry is likely to help in discriminating between normal and abnormal eyes. The thinnest corneal value (Thk Min ) was calculated over an 8-mm area.
The above-described parameters (Thk Min , SI f , Si b , R f , p f , RMS/A f , R b , p b , RMS/A b ) were taken into account and analyzed for the VKC and control group. All statistical analyses were performed using IBM SPSS v.19 (IBM Corp, Armonk, New York, USA).
First, the normal distribution of each index in both the VKC and control group was investigated using the Kolmogorov-Smirnov test for normality. Then a statistical description was provided, through mean and standard deviation for normally distributed indices and 1st, 5th, 50th, 95th, and 99th percentiles. Finally, statistical differences among groups were assessed for each of the normally distributed indices by the t test for means equivalence: nonparametric analysis of variance by means of the Mann-Whitney-Wilcoxon test was performed for non-normally distributed indices.
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