THE ROLE OF GENOMIC BIOMARKERS IN PREDICTING VISUAL OUTCOMES IN GLAUCOMA PATIENTS
DOI:
https://doi.org/10.66021/pakmcr685Keywords:
glaucoma; primary open-angle glaucoma; normal-tension glaucoma; genomic biomarkers; polygenic risk score; GWAS; CDKN2B-AS1; SIX6; TMCO1; CAV1/CAV2; MYOC; OPTN; TBK1; visual field progression; mean deviation slope; risk stratification; precision ophthalmology; Pakistan; cohort study; predictive modeling.Abstract
Objective: This cohort study was conducted to determine whether genomic biomarkers (single-variant markers and a polygenic risk score) predicted the rate of visual field loss and the final functional visual outcome among glaucoma patients managed at a tertiary hospital in the north-western region of Pakistan.
Methods: We assembled a longitudinal cohort of adults with primary open-angle glaucoma (POAG) and normal-tension glaucoma phenotypes who were followed under routine clinical care. Standard automated perimetry (24-2) was used to estimate progression as mean deviation (MD) slope (dB/year) and event-based deterioration. Blood samples were genotyped for established glaucoma-associated loci and aggregated into a multitrait glaucoma polygenic score informed by large genome-wide association studies. Multivariable mixed-effects and Cox regression models were fitted to test whether genomic markers predicted progression and poor visual outcomes after adjusting for baseline age, intraocular pressure (IOP) exposure, central corneal thickness, baseline MD, optic nerve head features, treatment escalation, and adherence proxies.
Results: Genomic burden was associated with faster functional decline. Patients within the highest genetic-risk stratum demonstrated steeper MD loss and a higher hazard of reaching advanced functional impairment compared with the lowest stratum, even after accounting for baseline disease severity and IOP-related factors. Variants and regions repeatedly implicated in POAG biology (including CDKN2B-AS1, SIX6, TMCO1, and CAV1/CAV2) contributed meaningfully to prediction when combined as a polygenic score. The incremental value of genetics was most evident in patients whose clinical risk profile appeared “intermediate,” where genomic stratification separated slow progressors from rapid progressors.
Conclusion: In this Pakistani tertiary-care cohort, genomic biomarkers—particularly an aggregated polygenic risk score—were associated with the pace of visual field deterioration and the probability of poor functional outcomes. These findings supported the feasibility of using genetics to personalize follow-up intensity and treatment targets in glaucoma care, alongside established clinical predictors.
