The Influence of Cone Location and Phenotype on the Risk and Rate of Keratoconus Progression

To assess if cone location and phenotype have an impact on the risk of keratoconus progression. Retrospective multi-centric cohort study. The baseline visit was used to classify cases according to cone location (based on thinnest pachymetry and maximum keratometry, <i>K</i>max) and phenotype. Cases were further labeled as stable or progressive depending on whether they fulfilled criteria for progression throughout the follow-up. Time from baseline to progression was noted. Univariate and multivariate mixed-effects models accounted for correlations between both eyes of the same patient and adjusted for <i>K</i>max and age at baseline. A total of 423 eyes from 250 patients was included, 48.0% (<i>n</i> = 203) labeled as progressive. Based on the location of thinnest pachymetry and <i>K</i>max, 72.1% (<i>n</i> = 305) and 60.8% (<i>n</i> = 257) respectively were classified as central. In univariate analysis, there were significant differences between groups (<i>p</i> &lt; 0.001), with central keratoconus more frequently associated with progression. However, after adjusting for <i>K</i>max and age at baseline in multivariate analysis, this association lost its statistical significance. Results were similar for cone location based on thinnest pachymetry adjusted for <i>K</i>max and age. In univariate analysis, there were significant differences between groups (<i>p</i> &lt; 0.001) in the proportion of each phenotype in the stable and progressive groups, with central “nipple” keratoconus more frequently associated with progression. This was lost after adjusting for <i>K</i>max and age in multivariate analysis. Kaplan–Meier survival analysis showed significant differences between phenotypes (<i>p</i> &lt; 0.001), with central nipple cones progressing more rapidly. Central keratoconus and central “nipple” phenotype are more frequently associated with progression, and at a higher rate, but are not independent predictors for progression beyond keratometry and age.