New Biomarker Associated with Glaucoma Severity
Glaucoma is a leading cause of blindness both in the United States and around the world. As the world’s population ages in the coming years, the incidence of the disease is expected to increase. Because of this, researchers are focusing on how to prevent the disease, how to diagnose it earlier and how to track its progression.
Recently, a company named Q BioMed made progress with the latter. It announced licensure of a diagnostic marker which can be used to gauge the severity of glaucoma. The biomarker, known as growth differentiation factor 15 (GDF15), has been studied at Washington University in St. Louis and found to correspond to the level of severity of glaucoma in a patient. A GDF15 test could help guide treatment decisions for patients to achieve the best outcomes.
When the GDF15 test becomes commercially available, it could be a major asset for ophthalmologists and their patients. At present, there is no single diagnostic test or examination to gauge or predict disease progression. However, understanding how the condition might progress in any particular individual is critical for preserving vision.
Ophthalmologists now rely on supplemental measures to evaluate how much neurodegeneration has occurred as a result of glaucoma. This makes it difficult to make accurate predictions and can incur significant cost because of multiple repeated tests.
GDF15 has a number of advantages as a biomarker, including early detection compared to clinical tests. As a result, it may soon become a standard lab test for patients with glaucoma, or even one for patients with suspected disease.
The Process of Discovering and Validating the GDF15 Biomarker
Rajendra Apte, MD, PhD, the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences at Washington University School of Medicine, discovered GDF15, which can be seen as a measure of damage to cells in the eye. GDF15 belongs to the transforming growth factor beta (TGF-beta) superfamily. Its expression seems to correlate with severity of glaucoma, as well as progression of the disease.
Already, the biomarker has been validated in both mouse and rat models of glaucoma and then subsequently confirmed in human patients. The biomarker makes it possible to get a sense of the neurological damage which has occurred as a result of increased intraocular pressure.
Reducing this pressure is the mainstay of treatment. However, its measure does not indicate the degree of damage already done. GDF15 offers a way to track survival of the retinal ganglion cells. Thus, it could be a more effective measurement of treatment response than intraocular pressure.
The research team behind the biomarker first noticed GDF15 levels increased as both mice and rats aged and developed optic nerve damage. Then, the team decided to test the hypothesis by analyzing the molecular makeup of fluid coming from patients’ eyes as they underwent surgery to treat a range of ocular issues, including glaucoma.
The analysis showed patients with glaucoma had significantly elevated levels of GDF15 in their ocular fluid compared to patients with other conditions. Furthermore, the researchers found higher levels of the molecule were associated with poorer functional outcomes. This is when they started to think of GDF15 as a potential biomarker for neuropathic damage in the eye.
Questions Remain Regarding the Utility of GDF15 in Glaucoma Treatment
The researchers do not believe GDF15 plays a role in causing retinal cells to die. This means it is not a therapeutic target, but rather a marker of cell stress. GDF15 seems to be more of an indicator of impending cell death. The research already done concerning GDF15 indicates it is an important marker of retinal cell damage.
The investigators have also identified a number of new avenues of exploration to help make the biomarker even more robust. The biomarker was validated in humans using post-surgical samples of ocular fluid, meaning they were tested only once. Moving forward, it will be important to see how the GDF15 values shift as the disease progresses. While there was a clear correlation between severity of disease and amount of GDF15 present, it is not clear how the biomarker accumulates as the disease progresses.
The other major question remaining to be answered is what happens to levels of GDF15 once patients start to lose significant amounts of their vision. The vision loss associated with glaucoma starts peripherally and moves centrally. The loss of vision correlates with death of neurons in the optic nerve caused by the pressure associated with glaucoma.
The researchers point out it is unclear whether GDF15 markers would decline as people experience significant vision loss, since the damage has already been done to these cells. If GDF15 is a marker of impending cell loss, it is feasible those levels will eventually decline in the most severe stages of the disease. At the same time, if something else is driving the marker, then levels may actually stay high.
