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    Biomarker research centers on early glaucoma diagnosis


    New biomarkers sought

    The goal of the program is to discover new biomarkers for glaucoma. It is not that glaucoma biomarkers don’t already exist. IOP, thinning of nerve fiber layers, visual field testing, and other changes are helpful and in use today, but they lack specificity and sensitivity, especially over shorter time scales.

    “If we could discover a very sensitive, very specific biomarker for glaucoma, we could avoid much of the vision loss that is associated with the disease today,” Dr. Dubra said. “Our research focus is to be able to diagnose glaucoma very early and detect the specific, minute changes that could allow us to reduce vision loss.”

    There is no shortage of biomarker candidates. Research teams are actively looking at metabolic changes, synapse loss, axon loss, glial activation, and vascular compromise. One of the most fundamental questions is whether there is a specific type of retinal ganglion cell (RGC) that shows changes first, at the earliest stages of glaucoma, and whether those changes can be detected. The answer appears to be yes.

    A bead model of glaucoma produces chronic increases in IOP. Animal studies have found that RGCs in the “off” sublaminal layer are strongly impacted by rising IOP with dendritic structures that are clearly deformed. This same layer is rich in vasculature and fits with other evidence showing how different laminal layers are affected depending on their degree of vascularization.

    Evidence to date suggests that early selective damage to connections in this “off” sublayer of the inner retina is a reliable biomarker for glaucoma. Human studies will begin later this year.

    Depth-resolved OCT spectroscopy is also emerging as a more useful tool than it has been in the past. New techniques use motion to generate contrast without the use of exogenous dyes, extract extremely high-resolution data on the relative oxygenation within specific layers of the retina and measure blood flow velocity.

    “For the first time, you can calculate how much oxygen the retina uses in specific locations,” Dr. Dubra said. “We may be able to see if regions affected by glaucoma show higher or lower oxygen consumption and whether there are changes over time.”

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