Association of myopia and intraocular pressure with retinal detachment in European descent participants of the UK Biobank cohort: a mendelian randomization study

Importance: Rhegmatogenous retinal detachment is a potentially sight-threatening condition. The role of myopia or intraocular pressure (IOP) in retinal detachment remains unclear.

Objective: To determine if myopia or IOP is associated with retinal detachment risk using genetic data.

Design, setting, and participants: Observational analyses and 2-sample mendelian randomization were used to evaluate the associations between myopia, IOP, and retinal detachment risk in European descent participants from the UK Biobank (UKBB) cohort (n = 405 692). For retinal detachment, a genome-wide association study on 4257 cases and 39 181 controls in the UKBB was conducted. Genetic variants associated with mean spherical equivalent (MSE) refractive error (n = 95 827) and IOP (n = 101 939) were derived using independent participants from the retinal detachment genome-wide association study. Recruitment to the UKBB occurred between 2006 and 2010, and data analysis occurred from February 2019 to March 2020.

Main outcomes and measures: The odds ratio (OR) of retinal detachment caused by per-unit increases in MSE refractive error (in diopters [D]) and IOP (in mm Hg).

Results: Of the 405 692 participants in the UKBB cohort, the mean (SD) age was 56.87 (7.96) years, the mean (SD) MSE was -0.31 (2.65) D, the mean (SD) corneal-compensated IOP was 16.05 (3.49) mm Hg, and 4253 participants (1.0%) had retinal detachment. Genetic analyses of the 4257 cases and 39 181 controls identified 2 novel retinal detachment genes: COL22A1 (lead single-nucleotide variant rs11992725; P = 4.8 × 10^-10) and FAT3 (lead single-nucleotide variant rs10765568; P = 1.2 × 10^-15). Genetically assessed MSE refractive error was negatively associated with retinal detachment (per-unit [D] increase in MSE refractive error: OR, 0.72; 95% CI, 0.69-0.76; P = 3.8 × 10^-44). For each 6-D decrease in MSE refractive error (representing the move of refractive error from emmetropia to high myopia), retinal detachment risk increased 7.2-fold (95% CI, 5.19-9.27). For per-unit (mm Hg) genetically assessed increase in IOP, the risk of retinal detachment increased by 8% (OR, 1.08; 95% CI, 1.03-1.14; P = .001).

Conclusions and relevance: This study provides genetic support for the assertion that myopia and IOP are associated with the risk of retinal detachment and that myopia prevention efforts may help prevent retinal detachment.