Are we ready for genetic testing for primary open-angle glaucoma?

Abstract

Following a dramatic reduction in the cost of genotyping technology in recent years, there have been significant advances in the understanding of the genetic basis of glaucoma. Glaucoma patients represent around a quarter of all outpatient activity in the UK hospital eye service and are a huge burden for the National Health Service. A potential benefit of genetic testing is personalised glaucoma management, allowing direction of our limited healthcare resources to the glaucoma patients who most need it. Our review aims to summarise recent discoveries in the field of glaucoma genetics and to discuss their potential clinical utility. While genome-wide association studies have now identified over ten genes associated with primary open-angle glaucoma (POAG), individually, variants in these genes are not predictive of POAG in populations. There are data suggesting some of these POAG variants are associated with conversion from ocular hypertension to POAG and visual field progression among POAG patients. However, these studies have not been replicated yet and such genetic testing is not currently justified in clinical care. In contrast, genetic testing for inherited early-onset disease in relatives of POAG patients with a known genetic mutation is of clear benefit; this can support either regular review to commence early treatment when the disease develops, or discharge from ophthalmology services of relatives who do not carry the mutation. Genetic testing for POAG at a population level is not currently justified.

Fig. 1

Conceptual diagrams for complex disease. Each circle represents an individual person; filled in circles are people affected by disease and hollow circles are unaffected controls. a and b–d are two different concepts for complex disease. First concept: a The arrows are risk factors (genetic or environmental); different colours represent different risk factors. It can be seen that none of the risk factors are present in all of the cases, and some of the risk factors that contribute to disease are present in controls. Second concept: b In this concept, each individual risk factor is sufficient to cause the disease. The different colours represent different subsets of disease which may or may not be clinically distinguishable. c If all cases are examined together, identifying each risk factor can be challenging as they are present only in subset of cases. d If the cases are subdivided in a biologically meaningful way, this can increase the power to identify risk factors despite the smaller sample size