A cross-sectional study was carried out to analyses the topographic, pachymetric and aberrometry variables obtained by rotary Scheimpflug camera (Pentacam® type) from patients diagnosed with keratoconus, subclinical keratoconus and normal corneas in the Ophthalmology Service at the Torrecárdenas University Hospital (Almería, Spain) between February 2018 and February 2019. The data have been collected from the Pentacam® clinical database.
Participants have been previously informed of the data to be taken and have signed an informed consent authorizing the use of their data anonymously. The ethical principles for medical research on human beings of the Declaration of Helsinki have been followed.
The sample size has been estimated with the Ene 3.0 calculator for the mean of a continuous variable (total corneal coma) in three pre-established strata. Thus, we based on the study by Prakash et al. [24] where values of total corneal coma aberration (µm) were obtained in normal patients (0.3±0.1), subclinical(early) keratoconus (0.5±0.3) and clinical keratoconus (2.1±1.3). The reference population is all patients over or equal to 18 years old with keratoconus in the province of Almeria. After consulting the Institute of Statistics and Cartography of Andalusia, the total population census is 706,672 inhabitants, with those under 18 years of age (143,523 inhabitants). Therefore, the total estimated population is 563,149 inhabitants. The number of keratoconus in this population would be 168 cases, if we consider that its prevalence is 30/100,000, according to the recent study by Fernández-Barrientos et al. [8] Estimated prevalence and clinical characteristics of keratoconus in the healthcare setting of the Hospital Costa del Sol, Spain. J Emmetropia 2014;5:15–21).To achieve a precision of 0.12 units in the estimation of a mean by means of a 95% bilateral confidence interval and assuming that the standard deviations of each stratum are those obtained in the previous study, it is necessary to include a total of 188 experimental units distributed among the 3 strata with proportions of 40% (75), 20% (38) and 40% (75).
A total of 205 eyes of 205 patients (only one eye per patient) was distributed in 3 groups
Group 1: Healthy patients without corneal pathology,
Group 2 Patients with early-stage keratoconus(ESKC). This group included patients with an eye with topographic signs of keratoconus and/or suspicious topographic findings under normal slit-lamp examination and keratoconus in the fellow eye as recently defined by Henriquez et al. [20]
Group 3 Patients with keratoconus(KC). They must present at least one biomicroscopic alteration of the anterior segment (central thinning with Fleischer's ring and Vogt's striae) and the topography compatible with corneal ectasia. In patients with bilateral keratoconus, one of the eyes had been taken randomly.
The exclusion criteria were to have any systemic or ocular pathology and any ocular surgical intervention, including intrastromal rings and cross-linking.
A complete ophthalmological examination was performed in all cases.
Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) were collected with Snellen's chart (decimal scale). Objective refraction obtained by an autorefractometer (KR8900, Topcon, Japan) biomicroscopy (Carl Zeiss Meditec AG, Jena, Germany) and fundus were examined.
A corneal topographic analysis was performed on all patients by the same trained physician, under the same dark conditions and a pupil diameter of 6 mm. Patients with soft contact lenses didn´t wear them for three weeks, and the gas-permeable rigid lenses for at least five weeks before the test. The examination was performed with the rotary camera Scheimpflug (Pentacam® AXL, Oculus Optikgeräte, Wetzlar, Germany).
The following variables were collected:
Corneal topography of the anterior face: minor curvature (K1), major curvature (K2), mean curvature (Km), maximum curvature (KMAX), asphericity (Q), vertical asymmetry index (VAI); corneal topography of the posterior face: minor curvature (K1), major curvature (K2), mean curvature (Km) and asphericity (Q), central corneal thickness (CCT), minimum corneal thickness (MCT) with its coordinates (x,y) mean square root of total aberrations (Total RMS), mean square root of high order aberrations (HOA RMS), secondary corneal astigmatism to 0º (Z22) and 45º (Z2-2), anterior horizontal coma to 0º, posterior horizontal coma to 0º, total horizontal corneal coma to 0º (Z3¹), anterior vertical coma to 90º, posterior vertical coma to 90º, total vertical corneal coma to 90º (Z3-1), trefoil to 0º (Z3-3), trefoil to 30º (Z33), tetrafoil to 0º (Z44), tetrafoil to 22.5º (Z4-4) and spherical aberration (Z40) and the Pentacam diagnostic indexes: BAD-D, IHR, PPI, ArtMax and IVA.
Statistical analysis was performed using the software for Windows SPSS (version 25.0, SPSS, Chicago, Illinois, USA) and R (version 3.5.1). A bivariate analysis was performed, previously checking the normality of the variables with the Kolmogorov Smirnoff test. The non-parametric Wilcoxon rank-sum test (Mann-Whitney test) was used for two samples and Kruskal Wallis test for more than two samples. For the binary logistic regression model, early keratoconus and normal groups were used as a dichotomous dependent variable, and stepwise method, direction forward-backwards and AIC criteria ( Akaike information criteria) were used to include all possible predictor variables and to eliminate those that didn´t add value to the study(according to AIC criteria). The binary regression model is expressed in the form of an algorithm :
Logit (p/1-p) =-a-x1β1- x2β2+ x3β3
Odds Ratio (OR) =e-a-x1β1- x2β2+ x3β3
a= constant
x1, x2, x3= coefficients of the model
β1, β2, β3= Variables of the model
p/1-p= Odds Ratio
Once the coefficients have been calculated, the model is validated by evaluating the variance influence factors (VIF), which indicate that the correlation between the variables is low (less than 2). The Hosmer-Lemeshow test evaluated the fit of the model ROC curve calculated the AUC (Area under the curve) and the confusion matrix (actual vs predicted group) estimated the accuracy, precision, sensitivity and specificity of the diagnostic indices and discrimination functions performed on the validation set