Inter-Relationships between Retinal Vascular Caliber, Retinal Nerve Fibre Layer Thickness and Glaucoma: A Mediation Analysis Approach.

Abstract

Purpose : To explore the inter-relationship between retinal vascular caliber, retinal nerve fibre layer (RNFL) and glaucoma; in particular, whether the relationship between narrower retinal vascular caliber and glaucoma is mediated by thinning of RNFL.

Methods : A total of 9,407 participants, including 253 glaucoma and 195 primary open-angle glaucoma (POAG) cases from the Singapore Epidemiology of Eye Diseases Study were included in this study. All participants underwent standardised examinations. Retinal vascular calibers were measured from retinal photographs using a computer-assisted program and summarised as central retinal artery and vein equivalents (CRAE and CRVE, respectively). Confocal scanning laser tomography was used to measure RNFL thickness. Glaucoma was defined according to the International Society for Geographical and Epidemiologic Ophthalmology criteria. Logistic regression analyses were used to determine the total and direct effects of retinal vascular calibers on glaucoma. Regression-based mediation analyses were used to evaluate the indirect effects of retinal vascular calibers on glaucoma through RNFL thinning. The proportion of effect mediated was calculated as the ratio of the indirect effect over total effect estimate.

Results : After adjusting for relevant covariates, narrower CRAE (per standard deviation [SD], 15.1µm decrease) was associated with glaucoma (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.06-1.38) and POAG (OR, 1.23; 95% CI, 1.06-1.43). Narrower CRVE (per SD, 21.6µm decrease) was associated with glaucoma (OR, 1.51; 95%CI, 1.32-1.73) and POAG (OR, 1.64; 95% CI, 1.41-1.91). In addition, there were significant indirect effects of CRAE narrowing on glaucoma (OR, 1.02; P<0.001) and POAG (OR, 1.03; P<0.001) through thinning of RNFL, and the proportion mediated by thinning of RNFL was 36.9% in glaucoma and 32.3% in POAG. Similarly, there were significant indirect effects of CRVE narrowing on glaucoma (OR, 1.03; P<0.001) and POAG (OR, 1.04; P<0.001) through thinning of RNFL, and the proportion mediated by thinning of RNFL was 12.9% in glaucoma and 12.3% in POAG.

Conclusions : Mediation analyses indicated that relationship between retinal vascular narrowing and glaucoma was partly mediated through RNFL thinning. These findings provide further mechanistic insights into the link between microvascular changes and glaucoma.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.