EyeLife: A prospective glaucoma screening study with double‐blind genetic pre‐screening conducted within the population‐based Lifelines cohort

Abstract

Purpose: Glaucoma screening potentially prevents blindness but is currently considered not cost effective due to insufficient screening test specificity given a low disease prevalence in the general population. Genetic pre‐screening could increase the prior probability (higher prevalence in a selected population). The aim of this study was to identify the relative risk of glaucoma in a subgroup of the general population with a high compared to one with a low genetic glaucoma risk.Methods: The study protocol has been published previously (PMID: 33413217). We invited 1600 participants from the European Lifelines cohort (n = 165 000) aged 55+. Participants belonged to either the highest or lowest 20% of a GWAS‐based genetic risk score distribution; subgroups had similar age and gender. Researchers and participants were blinded regarding subgroup allocation. All participants underwent frequency doubling perimetry (FDT), optical coherence tomography (OCT) of the peripapillary retinal nerve fibre layer, and fundus photography to assess the optic nerve head (ONH). Any abnormal test result resulted in an ophthalmic exam including gonioscopy. Participants were classified as definite (abnormal FDT and either abnormal OCT or ONH), probable (either abnormal FDT or abnormal OCT and ONH), or possible (normal FDT with either abnormal OCT or ONH) open‐angle glaucoma (OAG), or as healthy. We obtained the relative risk of combined definite and probable OAG compared to healthy, excluding possible OAG.Results: A total of 1031 participants responded (65%; 493 with high versus 538 with low risk). Of those, 31 (29 versus 2) were classified as definite and 28 (21 versus 7) as probable OAG. The prevalence of combined definite and probable OAG was 5.7%. The relative risk was 6.3 (95% CI 3.1–12.9).Conclusions: Genetic pre‐screening seems a promising way to increase the prior probability of glaucoma and thus make glaucoma screening more cost‐effective.