Shining a light on glaucoma: an interview with Dr Konstantinos Nikopoulos, Unilabs Genetics

Glaucoma is the leading cause of irreversible blindness worldwide. It comprises a group of eye conditions that can lead to progressive damage of the optic nerve, which is crucial for vision. The damage is often associated with increased pressure within the eye, known as intraocular pressure (IOP). However, glaucoma can occur even with normal IOP.

Risk factors for glaucoma include age (it's more common in older adults), family history, population background, and certain medical conditions like diabetes and high blood pressure.

On World Glaucoma Week, we have spoken to Dr Konstantinos Nikopoulos, Scientific Manager at the Department of Genetics at Unilabs Switzerland, to delve into this topic.

How does genetic testing contribute to identifying early symptoms or predicting disease progression in patients with glaucoma?

Genetic testing has become relatively inexpensive, and it is performed only once per lifetime. It enables the identification of pathogenic variants in specific genes (e.g., OPTN, MYOC), particularly in certain familial glaucoma cases, or of gene variations collectively linked to an increased risk of developing the disease. Therefore, subsequent to genetic testing, the adoption of a personalised medicine approach becomes a reality. This allows for the stratification of individuals carrying these genetic markers for proactive surveillance and, as circumstances dictate, intervention, with the objective of attenuating the disease's progression.

Are there specific genetic markers that correlate with the severity or progression rate of glaucoma symptoms?

Yes, there are several gene variants that have been documented for their specific ‘genotype-phenotype’ correlations or ‘endophenotypes’, meaning that a genetic marker can influence the clinical symptoms of a patient. Let’s consider for instance specific pathogenic variants within the MYOC gene, which exhibit strong correlations with the onset of severe glaucoma at an early age, contrasting with other variants predisposing individuals to milder forms emerging later in life. Additionally, individuals carrying CYP1B1 variants often exhibit a tendency towards aggressive bilateral disease and a high frequency of surgical interventions. While certain genetic markers may provide invaluable insights into disease prognosis and progression, the complex interplay between genetic predisposition and environmental factors remains crucial in the pathogenesis of glaucoma. Hence, the integration of genetic testing results plays a central role in modern ophthalmological practice, working hand in hand with other clinical parameters to inform personalised treatment modalities and management strategies.

What are some promising avenues of research in understanding the genetic basis of glaucoma and its implications for personalised medicine?

Research on the genetic basis of glaucoma and its implications for personalised medicine is undergoing rapid transformation. Notably, advances in artificial intelligence and machine learning, coupled with the expanding availability of genomic data, provide more power in constructing accurate risk prediction models aimed at grouping patients based on their susceptibility to developing glaucoma. Furthermore, significant progress in pharmacogenetics is facilitating the optimisation of glaucoma therapeutics through the creation of tailored treatment regimens. Such approaches not only enhance efficacy but also mitigate and minimise adverse effects for patients. Last but not least, ‘functional genomics, including gene expression studies, the elucidation of specific proteins, and molecular pathways function, contributes profoundly to revealing the pathogenesis of glaucoma. Consequently, these efforts may facilitate the identification of novel pharmaceutical targets with promising prospects for the management of this complex condition.

How might advances in genetic testing technology improve early detection and treatment outcomes for glaucoma patients in the future?

Glaucoma is a complex disease. The progress of genetic testing technology, encompassing both screening methodologies and ‘big’ data analysis, by means of AI and machine learning, has a dual impact. This collaboration enables the identification of individuals at elevated risk by constructing personalised risk profiles. This not only facilitates more targeted clinical surveillance but also fosters a deeper understanding of the disease progression. In the same line, advancing our understanding of the genetic basis of glaucoma and its pathophysiology at the molecular and cellular level holds significant promise for the development of novel, individualised, and more efficacious therapies. 

Overall, integrating genetic testing into glaucoma management holds great promise for improving early detection and treatment outcomes, ultimately preserving vision for longer and enhancing the quality of life for affected individuals.

Types of glaucoma

There are several types of glaucoma, but the two main broad categories are open-angle glaucoma and angle-closure glaucoma:

• Open-angle glaucoma: This is the most common type of glaucoma. It occurs when the drainage angle within the eye remains open but becomes less efficient over time, leading to a gradual increase in intraocular pressure. This increased pressure can damage the optic nerve.

• Angle-closure glaucoma: In this type, the drainage angle of the eye becomes blocked or closed, leading to a sudden increase in intraocular pressure. This is considered an emergency and requires immediate medical attention to prevent permanent vision loss.

Understanding the genetic basis of glaucoma 

While genetic testing for glaucoma susceptibility is not routinely performed, ongoing research aims to identify specific genetic markers associated with the disease. Understanding the genetic basis of glaucoma will further contribute to improved risk assessment, early detection, and personalised treatment approaches.

Let’s see how:

• Identification of gene mutations: Genetic testing can help identify specific mutations or variations in genes known to cause or to be associated with glaucoma. This information can provide insights into the underlying causes of the disease in individual patients and their families.

• Early detection and risk assessment: In cases where specific gene variants associated with glaucoma are identified, genetic testing can help assess the risk of developing the disease in asymptomatic individuals. This can be particularly valuable for individuals with a family history of glaucoma who may benefit from more frequent eye examinations and proactive management strategies.

• Personalised treatment approaches: Genetic testing results can inform personalised treatment approaches for individuals with glaucoma. Certain gene mutations may influence the choice of medications, surgical interventions, or other management strategies, allowing for more targeted and effective treatment.

• Research and clinical trials: Genetic testing data contribute to ongoing research efforts aimed at better understanding the genetic basis of glaucoma and developing new therapeutic interventions. Participation in clinical trials and research studies may be facilitated by genetic testing.