Clinical applications of molecular genetics research in glaucoma daily practice
Authors: Milla Elena 
Published: December 2022

Personalized medicine using genetic information to predict disease development and tailor preventive interventions is an evolving field. In the last decade, molecular genetic studies in glaucoma have experienced a great advance, partly due to the appearance of new diagnostic technologies such as high‐efficiency and rapid next‐generation sequencing (NGS) that allows the sequencing of gene panels in a short time, exomes or complete genomes. With these advances, the list of candidate genes associated with the diagnosis of POAG has greatly increased and there is increasing information about the molecular mechanisms underlying POAG. The new genes involved in the pathology of glaucoma are mainly related to oxidative stress, DNA repair mechanisms, mitochondrial DNA, sex hormones, etc. The study of loci associated with quantitative endophenotypic traits has also been proposed that would act as risk factors for the disease (pachymetry, axial length, anterior chamber depth, diameter of the retinal vessels, papillary excavation, etc.) that, when added together, would increase the risk of developing POAG.

On the other hand, exome sequencing can be useful for the detection of polymorphisms in genes associated with the individual response to medical treatment of glaucoma (pharmacogenic bases of glaucoma) and the possible success of filtering surgery in these patients (genetic bases of glaucoma). Early fibrosis in individuals with glaucoma.

Recent studies have described the existence of polymorphisms against the ocular pharmacological receptors of the drugs commonly used to treat glaucoma that would cause an absence of pharmacological response. These would be polymorphisms in genes encoding drug receptors for prostaglandin analogs (rs3766355; rs3753380) and topical beta‐blockers (rs1042714) and would provide valuable information on whether the patient will respond well to these drugs or will be resistant them and thus plan their antiglaucomatous treatment in a personalized and early manner. The main cause of surgical failure in patients with glaucoma is fibrosis of the conjunctival bleb. This may be due to acquired factors (prolonged use of topical medication causing inflammation of the ocular surface, eye drops with preservatives, dry eye, etc.), or genetic factors that would cause individual susceptibility to early fibrosis of the conjunctival bleb. In recent years, genes that present an overexpression at the conjunctival level in cases of early surgical failure have been described and studies have also been published on the existence of systemic and genetic humoral factors responsible for an individual hyperfibrosing genetic profile. Definitely. the study of exomes by means of NGS would allow us to quickly and effectively discover different aspects of the glaucomatous pathology of our patients: molecular diagnosis, detection of asymptomatic relatives, genetic counselling, type of appropriate hypotensive treatment and type of surgical technique that would increase surgical success. And so in the near future we will be able to personalize and administer early treatment that is key to stopping the destruction of the optic nerve in these patients.