Genetic Testing in Glaucoma

Glaucoma is a complex disease resulting from a mix of genetic and environmental factors. Family history is an important risk factor for glaucoma.

Glaucoma is a complex disease resulting from a mix of genetic and environmental factors. Family history is an important risk factor for glaucoma.

In primary open-angle glaucoma, the most common type of adult-onset glaucoma, close relatives of affected patients are almost 10 times more likely to develop glaucoma than in the general population, underscoring a strong genetic basis.

Glaucoma is a treatable (but not yet curable) condition and appropriate intervention may delay or prevent blindness. Population studies have shown that half of those affected with glaucoma remain undiagnosed, because there are usually no symptoms in the early stages. Genetic testing is a promising method of identifying at-risk individuals and providing them with early treatment opportunities.

Personalized Medicine

Personalized medicine using genetic information to predict disease development and to tailor preventive interventions for each patient is an evolving field. Current glaucoma therapies are effective in lowering IOP in patients with all types of glaucoma. Targeted therapies for gene-specific types of glaucoma are being investigated and may provide an additional treatment strategy; however, the proportion of patients with a clearly defined genetic cause for glaucoma is relatively small at present.

Genome-wide association studies (GWAS) with high throughput DNA genotyping of hundreds to thousands of subjects in clinical datasets, are a broadly used approach to identify genomic regions associated with a specific disease or phenotype. GWAS utilizes several million single nucleotide polymorphisms (SNPs) from an individual sample for analysis. This approach has been used to identify the chromosomal location of thousands of inherited disorders or phenotypes.

Currently, next generation high-throughput DNA sequencing technology is in high use in research and diagnostic testing laboratories to sequence the complete coding sequence of the human genome (exome), or the human genome in its entirety. These technologies offer a powerful approach to identify causal genetic variants for many rare and common genetic disorders, including primary open-angle glaucoma.

Current Recommendations

Current recommendations for genetic testing of diseases in general and for ophthalmic diseases in particular, are to develop individual or screening panels for known implicated genes with published mutations for the diseases. Sequenced genes with known functional and protein structural change associations can be used in genetic counseling and the development of specific treatments. As an example, the prevalence of Myocilin mutations in glaucoma cases with severe visual field loss is significantly greater than in non-advanced glaucoma patients. Identifying individuals who have Myocilin mutations provides an opportunity to screen at-risk clinically unaffected relatives and to reduce glaucoma blindness through early management and intervention.

The American Academy of Ophthalmology has published guidelines for genetic testing in eye disorders. Its main points are that genetic testing should only be offered to patients with clinical findings suggestive of a “Mendelian disorder,” where causative gene(s) have been identified and validated scientifically. Direct-to-consumer genetic testing is discouraged, and genetic counseling before and after any genetic test is recommended. Unnecessary parallel testing should be avoided and only the most specific test(s) available, based on the patient’s clinical findings, should be ordered.


Article by Terri L. Young, MD, MBA.
First published May 1, 2018; Reviewed April 22, 2022.

Terri L. Young, MD, MBA

Terri L. Young, MD, MBA

Terri L. Young, MD, MBA is the Peter A. Duehr Professor of Ophthalmology, Pediatrics, and Medical Genetics, and Chair of the University of Wisconsin Department of Ophthalmology and Visual Sciences. An internationally renowned physician-scientist, she studies the genetics of refractive errors, childhood glaucoma, and other inherited ocular disorders.