Purpose
To demonstrate whether posterior polymorphous corneal dystrophy (PPCD) associated and not associated with mutations in the zinc finger E-box binding homeobox 1 (ZEB1) gene is characterized by steep corneal curvatures.
Methods
Slit lamp biomicroscopic examination and corneal topographic imaging were performed for all available patients with posterior polymorphous corneal dystrophy and unaffected family members. Steep corneal curvatures were defined as average keratometry values greater than 48.0D in each eye. Eyes in which penetrating keratoplasty was performed prior to topographic imaging were excluded. Saliva or blood was collected from each individual for isolation of genomic DNA and automated sequencing of the ZEB1 gene.
Results
Corneal topographic imaging and ZEB1 screening were performed for 38 individuals (27 affected and 11 unaffected) from 23 families with PPCD. Seven of the 27 affected individuals were found to have mutations in the ZEB1 coding region, while screening of the promoter and coding regions in the remaining 20 individuals failed to reveal a mutation in the ZEB1 coding region. Ten of the 38 individuals (26.3%) were measured as having average keratometry values greater than 48.0D in each eye: 10/27 (37.0%) individuals with PPCD (6/7 individuals with ZEB1 mutations (85.7%) and 4/20 individuals with PPCD but without ZEB1 mutations (20.0%)) and 0/11 unaffected individuals (Fisher’s exact test: p=0.037 for Unaffected vs. affected; p=0.0042 for ZEB1 mutation vs. without ZEB1 mutation). The mean keratometry value averaged for both eyes of affected individuals measured 48.2D as compared to 44.1D for unaffected family members (t-test p value = 0.029). The affected individuals with ZEB1 mutations demonstrated a mean keratometry value averaged for both eyes of 53.3D, as compared to affected individuals without ZEB1 mutations (46.5D) (t-test: p value = 0.0044).
Conclusions
While PPCD is considered a corneal endothelial dystrophy, the identification of abnormally steep corneal curvatures in 25-30% of affected individuals, and in 85-90% of affected individuals with ZEB1 mutations, indicates that ZEB1 may play a role in corneal stromal development and/or physiology as well.
Keywords: 481 cornea: endothelium •
484 cornea: stroma and keratocytes •
539 genetics