Purchase this article with an account.
Claire Lixian Wong, Ekaterina Yonova, Katie M Williams, Mark James Simcoe, Diana Kozareva, Christopher J Hammond; Keratoconus Endophenotypes in a Healthy Aging Population. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3558.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Keratoconus is a complex condition; little is known about genetic factors underlying its susceptibility. Use of disease endophenotypes in population-based studies has identified genetic variants associated with various eye conditions, such as central corneal thickness (CCT) and keratoconus. This study aimed to access topographic measures that have been suggested as keratoconus risk indices – Keratoconus Prediction Index (KPI), apical gradient of curvature (AGC) and Symmetry Index (SI) – as possible endophenotypes in a healthy aging population.
Corneal topography and wavefront data from the Visionix VX120 autorefractor was analysed for 1430 twins (91% female, mean age 58.9, age range 18.5-91.7) from the TwinsUK cohort. STATA14 was used for exploring normality tests, correlations (Pearson, Spearman and Lin’s concordance correlation coefficients), association between age, CCT, and rank normalised AGC and SI (linear regression), and for conducting t-test for differences in means of predictors between KPI groups. Falconer’s formula was used to calculate broad-sense heritability (H2) for topographic measures in 414 monozygotic and 300 dizygotic twin pairs.
CCT was normally distributed (P=0.3), had a mean [SD] of 537.4µm [34.2µm], decreased with age (β=-0.17, P=0.01), and had a H2 of 0.72. AGC and SI were not normally distributed (P<0.0001), did not vary with age, had median [range] of 1.3 [-16.1:19.6] and 0.33 [-14.2:15.5], and had a H2 of 0.12 and 0.37 respectively. AGC and SI were not correlated with CCT or KPI but were weakly correlated with each other (rho=0.13). KPI followed trimodal distribution with 30% of participants having at least one eye predicted to be affected, although none of them had keratoconus. These individuals were on average older, had thinner corneas and lower K (P=0.003, P=0.02 and P<0.0001 respectively). The H2 of KPI (rho_c) was 0.60. Correlation between both eyes was strong for all variables: CCT (r2=0.82), AGC and SI (rho=0.62 both), and KPI (rho_c=0.55).
This study shows that although KPI is heritable, it is a poor keratoconus endophenotype as it mislabels 30% of individuals as cases, and is also a semi-quantitative measure. While AGC and SI had better distributions, they had lower heritability and did not strongly correlate with KPI or other predictors. Although CCT is known to not be an ideal endophenotype, it may still be the most reliable endophenotype for keratoconus to date.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only