Patients and sampling
This comparative study was performed in 2020 at Noor Ophthalmology Hospital in Tehran. The cases were mothers with children with Down syndrome (MDS); they were selected from a study of DS children, whose methodology has already been described.12 Women in the control group were mothers with normal children (MNC); these were selected from the hospital staff and visitors to match the MDS group in terms of maternal age at delivery. Any case with a history of eye surgery was excluded from the study.
Examinations
All participants underwent a comprehensive ophthalmic examination using slit-lamp biomicroscopy (Haag-Streit, Koniz, Switzerland). Uncorrected (UDVA) and corrected (CDVA) distance visual acuity assessment was performed using SC-2000 Chart (Nidek Co., Tokyo, Japan) and retinoscopy was done using HEINE BETA 200 with ParaStop (HEINE Optotechnik, Herrsching, Germany).
Corneal tomography was assessed using Pentacam HR (software version 6.08r30, data management version 1.21r43; Oculus Optikgeräte GmbH, Wetzlar, Germany) and corneal biomechanics were measured using Corneal Visualization Scheimpflug Technology (Corvis-ST; software version 6.08r30, data management version 1.5r1902; Oculus Optikgeräte GmbH, Germany). All tests were performed between 8 am and 12 noon by two optometrists (one experienced optometrist for each device).
Imaging with Pentacam was repeated until quality specification “OK” (minimum valid data: 93.0%) was reached. Extracted Pentacam indices included the minimum corneal thickness (MCT), maximum Ambrósio's relational thickness (ART-max), Belin Ambrósio display-total deviation (BAD-D), maximum keratometry in the central 8.0 mm (Kmax), average keratometry in the 3.0 mm zone around the steepest point (Zonal Kmax-3mm), inferior-superior asymmetry (I-S value), the anterior radius of curvature centered on the thinnest point (ARC), the posterior radius of curvature centered on the thinnest point (PRC), index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), center keratoconus index (CKI), index of height asymmetry (IHA), index of height decentration (IHD), anterior elevation at the thinnest point from the 8mm best-fit-sphere (AE-TP_8mmBFS), posterior elevation at the thinnest point from the 8mm best-fit-sphere (PE-TP_8mmBFS), irregularity index, anterior asphericity (Q-value), posterior Q-value, and pentacam random forest index (PRFI).
Extracted indices from the Corvis-ST included the tomographic biomechanical index (TBI), stiffness parameters at first applanation (SP-A1), deformation amplitude ratio at 1 mm (DA ratio-1mm), deformation amplitude ratio at 2 mm (DA ratio-2mm), integrated radius-1mm, highest concavity deformation amplitude (HC deform. ampl.), highest concavity deflection amplitude (HC deflec. amp.), biomechanical corrected intraocular pressure (bIOP), Peak Distance (PD), and radius.
Definitions
In both groups, corneas were categorized into KC, “mild or fruste” KC - which can be interpreted as with high susceptibility for ectasia progression, and normal subgroups based on ranges of ectasia indices as follows:
- KC: clinical sign (Fleischer ring, Vogt striae, Munson sign, apical thinning, or Rizutti sign) + at least one abnormal tomographic or biomechanical index (BAD-D> 3.0 standard deviation of mean,13 ART-max <339 μm,14 Kmax> 48.0 diopters (D),15 I-S value> 1.9 D,16 and TBI> 0.79.17)
- “Mild or fruste” KC: no clinical sign + abnormal tomographic or biomechanical index (BAD-D> 1.6 standard deviation of mean,13 ART-max <339 μm,14 Kmax> 47.2 D,15 I-S value> 1.4 D,16 or TBI> 0.39.17)
- Normal: all others.
Ethical consideration
The Ethics Committee of Tehran University of Medical Sciences approved the study (ID: IR.TUMS.MEDICINE.REC.1399.772). The aims and methods of the study were explained to the participants and written informed consent was obtained. The study adhered to the Helsinki Declaration at all stages.
Statistical analysis
Statistical analysis was performed using SPSS version 21 (IBM Corp., Armonk, NY, USA). The sample size was determined 56 cases in each group using n = 2(Zα/2+Zβ)2 х σ2 / d2 where the α=0.05, β=0.01, σ=1.0D for Zonal Kmax-3mm, and d=1.5D. Bonferroni’s correction was not applied to maintain a power of 99% for comparing indices between groups. In the analysis, assuming that the abnormality would be unilateral or asymmetrically bilateral,18 both right and lefts eyes were entered in the analysis. Binary generalized estimating equations (GEE) were used to compare the prevalence of KC and early KC between the two groups (MDS and MNC). For normal subgroups of MDS and MNC, linear GEE was used to compare mean values of the indices. In the analysis, fellow-eye correlations were applied using an unstructured correlation matrix.