Genetic risk score is associated with retinal nerve fiber layer thickness and severe glaucoma in Japanese normal-tension glaucoma patients

Abstract

Purpose : To investigate the association between genetic risk score (GRS) and the presence of normal-tension glaucoma (NTG; defined by peak intraocular pressure < 22 mmHg) in Japanese patients, and to determine whether GRS was related to retinal nerve fiber layer (RNFL) thickness and mean deviation (MD).

Methods : This study comprised 455 control subjects and 384 NTG patients. Weighted and unweighted GRS scores were constructed based on findings in 3 SNPs previously reported to be associated with primary open-angle glaucoma, including rs2157719 (CDKN2BAS-1), rs33912345 (SIX6) and rs9913911 (GAS7), in Japanese subjects (Shiga Y et al. PLoS ONE, 2018). Peripapillary RNFL thickness was measured with optical coherence tomography (3D OCT 2000, Topcon, Tokyo, Japan). Visual field parameters, including MD, were assessed with the 24-2 test program of the Humphrey Field Analyzer, with the worse eye of each subject being used for the analysis. Linear and logistic regression analyses were used to examine the association of GRS with NTG and RNFL thickness.

Results : GRS was associated with NTG (odds ratio (OR): 1.60, 95% CI: 1.23-2.09, p < 0.001) after adjusting for age and gender. In addition, GRS was significantly associated with a decrease in total peripapillary RNFL thickness of 1.53 μm (p = 0.03). When the peripapillary RNFL was further divided into superior, inferior, nasal and temporal quadrants and assessed separately, GRS was associated with a decrease in thickness of 2.61 μm (p = 0.02) superiorly, but not in other quadrants (p = 0.06 – 0.86). Furthermore, GRS was significantly associated with the presence of severe visual field damage (defined as MD ≤ -20 dB) (OR: 1.39, 95% CI: 1.07 – 1.80, p < 0.01) after adjusting for age. We obtained similar results for weighted and unweighted GRS.

Conclusions : These results suggest that an aggregation of multiple glaucoma-associated SNPs can reveal NTG patients with increased susceptibility to optic nerve head degeneration.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.