Abstract

In this retrospective cohort study, we recruited 5,025 patients (9,341 eyes) with early keratoconus between January 2011 and November 2020. Genetic data from 926 patients was available. We evaluated both change in keratometry or CXL as indices of progression and used the Royston-Parmar method on the proportional hazards scale to generate a prognostic model. We calculated hazard ratios (HR) for each significant covariate, with explained variation and discrimination. After exclusions, model-fitting comprised 8,701 eyes, of which 3,232 underwent CXL. For early keratoconus CXL provided a more robust prognostic model than keratometric progression. The final model explains 33% of the variation in time-to-event age HR [95% confidence limits] 0.9 [0.90-0.91], maximum anterior keratometry (Kmax) 1.08 [1.07-1.09], and minimum corneal thickness 0.95 [0.93-0.96] as significant covariates. Single nucleotide polymorphisms (SNPs) associated with keratoconus (n=28) did not significantly contribute to the model. The predicted time-to-event curves closely followed the observed curves during internal-external validation. A prognostic model to predict keratoconus progression could aid patient empowerment, triage and service provision. Age at presentation is the most significant predictor of progression risk. Candidate SNPs associated with keratoconus do not contribute to progression risk.

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