Genetic Risk of Cardiovascular Disease Is Associated with Macular Ganglion Cell–Inner Plexiform Layer Thinning in an Early Glaucoma Cohort

Henry Marshall, Sean Mullany, Xikun Han, Ella C. Berry, Mark M. Hassall, Ayub Qassim, Thi Nguyen, Georgina L. Hollitt, Lachlan S. W. Knight, Bronwyn Ridge, Joshua Schmidt, Caroline Crowley, Angela Schulz, Richard A. Mills, Ashish Agar, Anna Galanopoulos, John Landers, Paul R. Healey, Stuart L. Graham, Alex W. HewittRobert J. Casson, Stuart MacGregor, Owen M. Siggs, Jamie E. Craig

Research output: Contribution to journalArticlepeer-review

Abstract


Purpose: To evaluate the association between genetic risk for cardiovascular disease and retinal thinning in early glaucoma.

Design: Prospective, observational genetic association study

Participants: Multicohort study combining a cohort of patients with suspect and early manifest primary open-angle glaucoma (POAG), a cohort of patients with perimetric POAG, and an external normative control cohort.

Methods: A cardiovascular disease genetic risk score was calculated for 828 participants from the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study. Participants were characterized as showing either predominantly macular ganglion celleinner plexiform layer (GCIPL), predominantly peripapillary retinal nerve fiber layer (pRNFL) or equivalent macular GCIPL and pRNFL spectral-domain OCT thinning. The cardiovascular disease genetic risk scores for these groups were compared to an internal reference group of stable suspected glaucoma and of an external normative population. Replication was undertaken by comparing the phenotypes of participants from the Australia New Zealand Registry of Advanced Glaucoma (ANZRAG) with the normative control group.

Main Outcome Measures: Spectral-domain OCT and Humphrey Visual Field (HVF) change.

Results: After accounting for age, sex, and intraocular pressure (IOP), participants with predominantly macular GCIPL thinning showed a higher cardiovascular disease genetic risk score than reference participants (odds ratio [OR], 1.76/standard deviation [SD]; 95% confidence interval [CI], 1.18e2.62; P ¼ 0.005) and than normative participants (OR, 1.32/SD; 95% CI, 1.12e1.54; P ¼ 0.002). This finding was replicated by comparing ANZRAG participants with predominantly macular GCIPL change with the normative population (OR, 1.39/SD; 95% CI, 1.05e1.83; P ¼ 0.022). Review of HVF data identified that participants with paracentral visual field defects also demonstrated a higher cardiovascular disease genetic risk score than reference participants (OR, 1.85/SD; 95% CI, 1.16e2.97; P ¼ 0.010). Participants with predominantly macular GCIPL thinning exhibited a higher vertical cup-todisc ratio genetic risk score (OR, 1.48/SD; 95% CI, 1.24e1.76; P < 0.001), but an IOP genetic risk score (OR, 1.12/ SD; 95% CI, 0.95e1.33; P ¼ 0.179) comparable with that of the normative population.

Conclusions: This study highlighted the relationship between cardiovascular disease and retinal thinning in suspect and manifest glaucoma cases.
Original languageEnglish
Article number100108
Number of pages12
JournalOphthalmology Science
Volume2
Issue number1
DOIs
Publication statusPublished - Mar 2022

Keywords

  • Cardiovascular disease
  • Glaucoma
  • Macular GCIPL
  • Paracentral visual field
  • Retinal thinning

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