GRF update: Adaptive optics and glaucoma biomarkers

San Francisco-In a rapid-fire update, Alfredo Dubra, PhD, presented new glaucoma findings using adaptive optics and glaucoma biomarkers. Dr. Dubra, assistant professor and co-director, Advanced Ocular Imaging Program, Medical College of Wisconsin, highlighted recent results from the “truly collaborative” research that he and three other recipients-Jeffrey Goldberg, MD, PhD; Andrew D. Huberman, PhD; and Vivek J. Srinivasan, PhD-of the Glaucoma Research Foundation’s Catalyst for a Cure grants have produced in less than 2 years. 

The Catalyst for a Cure program is unique in that researchers are encouraged to work and think out of their fields and not follow narrow hypotheses. 

None of the four researchers are “glaucoma experts,” said Dr. Dubra at the 3rd Annual Glaucoma 360 New Horizons Forum here. 

The goal of their collaboration was to define new sensitive and specific biomarkers of the disease of glaucoma. They considered various aspects of IOP, thinning of nerve fibers, and microperimetry changes and how these contribute to loss of vision in glaucoma. Their candidates for new tools for the diagnosis of very early glaucoma include metabolic chemicals, synapse loss, axon injury, glial activation, and vascular compromise.  

Dr. Dubra noted the retinal ganglion is affected early on in the glaucoma disease process so they set out to find ways to measure changes at this locus. Using animal models to produce chronic injury, they found changes occur in the Off-sublamina, a sublayer in the retina that is vascular rich.

For the first time, Dr. Dubra said they can measure oxygen use, saturation, and flow speed in the inner retina layer. He expects to apply these techniques soon in humans. 

Ophthalmic adaptive optics now allow researchers to view the side of the eye and photograph individual cells. Large epiretinal structures have subsequently been identified. Split detectors show a mosaic of photoreceptors on the inner segments.

The researchers plan to apply these techniques not only in glaucoma but in retinitis pigmentosa and gene therapy as well. They eventually hope to study the transitions that occur in the development of glaucoma and the actual temporal development of disease.

An exciting aspect of adaptive optics is the method requires no exogenous dye to observe the movement of individual blood cells.  

Endothelial cells may serve as biomarkers. Split-detection vascular imaging in humans is currently being used without dyes to visualize an array of microaneurysm morphologies, which are more diverse than previously thought, Dr. Dubra said. 

The future of the Catalyst for Cure research collaborations includes development of tools to visualize and measure the individual cell’s response to glaucoma therapies. The researchers aim to decipher the retinal ganglion cellular metabolism in vivo and the structural and metabolic changes in unprecedented detail.  

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