The Association of Physical Activity with Glaucoma and Related Traits in the UK Biobank

Abstract

Purpose: To examine the association of physical activity (PA) with glaucoma and related traits, to assess whether genetic predisposition to glaucoma modified these associations, and to probe causal relationships using Mendelian randomization (MR).

Design: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia.

Participants: UK Biobank participants with data on self-reported or accelerometer-derived PA and intraocular pressure (IOP; n = 94 206 and n = 27 777, respectively), macular inner retinal OCT measurements (n = 36 274 and n = 9991, respectively), and glaucoma status (n = 86 803 and n = 23 556, respectively).

Methods: We evaluated multivariable-adjusted associations of self-reported (International Physical Activity Questionnaire) and accelerometer-derived PA with IOP and macular inner retinal OCT parameters using linear regression and with glaucoma status using logistic regression. For all outcomes, we examined gene-PA interactions using a polygenic risk score (PRS) that combined the effects of 2673 genetic variants associated with glaucoma.

Main outcome measures: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and glaucoma status.

Results: In multivariable-adjusted regression models, we found no association of PA level or time spent in PA with glaucoma status. Higher overall levels and greater time spent in higher levels of both self-reported and accelerometer-derived PA were associated positively with thicker mGCIPL (P < 0.001 for trend for each). Compared with the lowest quartile of PA, participants in the highest quartiles of accelerometer-derived moderate- and vigorous-intensity PA showed a thicker mGCIPL by +0.57 μm (P < 0.001) and +0.42 μm (P = 0.005). No association was found with mRNFL thickness. High overall level of self-reported PA was associated with a modestly higher IOP of +0.08 mmHg (P = 0.01), but this was not replicated in the accelerometry data. No associations were modified by a glaucoma PRS, and MR analyses did not support a causal relationship between PA and any glaucoma-related outcome.

Conclusions: Higher overall PA level and greater time spent in moderate and vigorous PA were not associated with glaucoma status but were associated with thicker mGCIPL. Associations with IOP were modest and inconsistent. Despite the well-documented acute reduction in IOP after PA, we found no evidence that high levels of habitual PA are associated with glaucoma status or IOP in the general population.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Glaucoma; Intraocular pressure; OCT; Physical activity; UK Biobank.

Figure 1.

Flow diagram outlining eligible UK Biobank participants available for this study. HES = Hospital Episode Statistics; ICD = International Classification of Diseases; IOP = intraocular pressure; IPAQ = International Physical Activity Questionnaire; PCA = principal components analysis.

Figure 2.

Graphs showing difference in measures of inner macular thickness by quartile of time spent in various levels of self-reported physical activity using the International Physical Activity Questionnaire (IPAQ): (A) overall IPAQ physical activity (PA) level, (B) by quartile of IPAQ sedentary behavior, (C) by quartile of IPAQ light activity, (D) by quartile of IPAQ moderate activity, (E) by quartile of IPAQ vigorous activity, and (F) by quartile of IPAQ total activity. MET = metabolic equivalent of task; mGCIPL = macular ganglion cell—inner plexiform layer; mRNFL = macular retinal nerve fiber layer; Ref = reference.

Figure 3.

Graphs showing difference in OCT parameter thickness by quartile of time spent in various levels of accelerometry-derived physical activity (PA): (A) by quartile of sedentary behavior (accelerometer, minutes per week), (B) by quartile of light activity (accelerometer, minutes per week), (C) by quartile of moderate activity (accelerometer, minutes per week), and (D) by quartile of vigorous activity (accelerometer, minutes per week). mGCIPL = macular ganglion cell—inner plexiform layer; mRNFL = macular retinal nerve fiber layer; Ref = reference.