Glaucoma Severity May Be Linked To Genetic Biomarkers

Checking for glaucoma
Checking for glaucoma
Deep sequencing may provide diagnostic and therapeutic targets to identify progressive POAG and provide early intervention.

Rho guanine nucleotide exchange factor 4 (ARHGEF4) and Fibronectin type III domain containing 3B (FNDC3B) are genes that may be associated with primary-open angle glaucoma (POAG) severity, according to research published in Experimental Eye Research. Individuals with these gene types may be more likely to experience more severe glaucoma, the investigators suggest. 

Researchers conducted a study of 40 patients with POAG to determine whether aqueous humor biomarkers could be linked with glaucoma progression. They stratified participants into 2 groups; stable POAG (n=20, mean age 74±7.36 years, 50% women) and uncontrolled POAG (n=20, mean age 75±13.69 years, 50% women). Investigators performed standard ophthalmic exams, pneumotonometry, obtained optic nerve images via spectral domain optical coherence tomography (SD-OCT), and collected aqueous humor samples for genetic profiling comparisons. 

Overall, researchers identified 21 candidate genes differentially expressed in progressive POAG patients compared with the stable group. Among the 21 identified genes, they reported that 5 were related to glaucomatous phenotypes (FND3CB, CLU, PCSK6, Celsr1, and ARHGEF4) and 3 were related to glaucoma suspect (ADCY6, GNAI2, and DNAH9). ARHGEF4 and FNDC3B were associated with POAG severity. 

“POAG is heterogeneous in etiology,” the researchers explain. “[This] study may provide diagnostic and therapeutic targets to identify and early treat progressive POAG.”

Study limitations include a small sample size, single center design, and possible confounding due to glaucoma medications. 


Zhao M, Ma P, Xie Q, et al. Biomarkers for primary open-angle glaucoma progression. Exp Eye Res. Published online March 5, 2022. doi:10.1016/j.exer.2022.109025