Genetic Susceptibility Variations and Visual Field Progression in Chinese Patients with Primary Angle Closure Glaucoma

Abstract

Purpose: Recently three susceptibility loci (rs3753841 in COL11A1, rs1015213, and rs11024102 in PLEKHA7) were found to be associated with primary angle closure glaucoma (PACG) through a genome-wide association study (Vithana EN et al, Nat Genetics 2012). We now investigate the contribution of these three loci on visual field (VF) progression in PACG patients with longitudinal VF data.

Methods: This was a retrospective case-only analysis in which PACG patients of Singaporean Chinese descent who had at least 5 years of follow-up and at least 5 VF tests (SITA 24-2, Carl Zeiss Meditec, Dublin, CA) were included. These patients had been previously genotyped for the 3 genetic variants. VF analysis was performed using pointwise linear regression (PROGRESSOR, Medisoft, Ltd, Leeds, England). Outcome measures were VF progression defined as 2 or more adjacent progressing points (slope p<0.01) in the same hemifield; and mean slope of sensitivity loss.

Results: A total of 355 eyes from 222 subjects were studied. The mean (SD) number of VF tests performed was 9.37 (4.15) and the mean (SD) duration of follow-up was 10.47 (3.13) years. For COL11A1 rs3753841, 164 eyes were from wildtype subjects while 139 and 52 eyes were from heterozygous and homozygous variants, respectively. The rate of VF progression of eyes that were wild-type, heterozygous and homozygous for COL11A1 was 14.02%, 9.35% and 3.85%, respectively (per allele odds ratio=0.56, P=0.03), although this observation was non-significant when corrected for multiple testing. The mean slope of sensitivity loss in the entire VF of eyes that were wild-type, heterozygous and homozygous for COL11A1 did not show significant difference (P = 0.77) and neither did the mean slope of sensitivity loss among the progressing points (P = 0.89). No significant difference was found in the rate of progression, mean slope of sensitivity loss in the entire VF or among the progressing points for the other two loci.

Conclusions: We did not observe evidence of association between the three PACG susceptibility loci and progression of VF loss in this cohort of PACG patients drawn from the original GWAS study. We acknowledge that our current sample collection may be under-powered to detect such effect sizes with regards to VF progression.

Keywords: 539 genetics • 758 visual fields