Abstract
Purpose :
We have previously described an updated and multi-trait polygenic risk score (PRS) for keratoconus. This study aims to interrogate the multi-trait PRS' ability to predict incident or longitudinal change in keratoconus phenotypes in a community-based cohort of young adults.
Methods :
Community-based young adults (age 18–30 years) underwent Pentacam imaging and genotyping. Additionally, a subset of participants returned for follow-up imaging 8 years later. Participants were genotyped and a multi-trait PRS, comprising genetic markers for keratoconus, central corneal thickness, and corneal resistance factor, were generated for each participant. Keratoconus was defined as a Belin/Ambrosio enhanced ectasia display (BAD-D) z-score of ≥2.6 based on Pentacam imaging. Associations between keratoconus phenotypes and PRS were explored using logistic or linear regression as appropriate, with adjustments for age, sex, genotyping array, and genetic ancestry. Participants who wore orthokeratology lenses, had undergone corneal surgery, or were of non-European descent were excluded from the analyses.
Results :
Of the 1,488 participants examined (51% female), prevalence of keratoconus was 2.5% (95% confidence interval [CI]= 1.95–3.6). In the cross-sectional analysis, each z-score increase in PRS was associated with a worse BAD-D score by 0.13 (95%CI= 0.08–0.18) and 1.6 increased odds of keratoconus (95%CI= 1.13–2.33). For the longitudinal study, data from 609 participants were available (52% female). The 8-year incidence of keratoconus was 2.6% (95%CI=1.3–4.0). Participants in the highest PRS decile were more likely to have incident keratoconus compared to the rest of the cohort (odds ratio= 3.85, 95%CI= 1.21–12.22). For each z-score increase in PRS, 8-year change in BAD-D score worsened by 0.11 (95%CI= 0.04 to 0.17).
Conclusions :
A PRS for keratoconus could be useful in predicting incident keratoconus and progression, demonstrating its potential utility in clinical settings to identify patients at high risk of post-surgery ectasia or those that may benefit most from keratoconus intervention.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.