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Vascular dysfunction in patients with glaucoma includes disturbances of blood pressure, perfusion pressure, and reduced blood flow within the retinal, optic nerve head (ONH), choroidal, and retrobulbar blood circulations.1 Loss of vasoreactivity and the ability to sufficiently dilate and constrict blood vessels according to localized tissue needs may result in chronic ischemia and ultimately retinal ganglion cell loss. Previous in-vivo hyperoxia testing models identified stress-induced reductions of volumetric blood flow to the retina in patients with glaucoma who failed to vasoconstrict compared to healthy controls.2
In the current study, Chen and colleagues assessed baseline differences and change in erythrocyte velocities in eyes following brief hyperoxia administration in glaucoma patients, glaucoma suspects, and healthy controls. The authors found hyperoxia significantly increased erythrocyte velocities in glaucoma suspects and controls, however, biomarker speeds decreased in glaucoma patients, likely due to impaired autoregulation. The authors emphasize the observed differences in vasoreactivity occurred only in retinal arterioles and not venules, suggesting their function as resistance vessels during healthy autoregulation.
A strength of the study is the ability to assess blood speed in vessels as small as 30 microns and a focus on the localized impact of vascular dysfunction to surrounding tissues. The authors present a unique example of impaired autoregulation in a blood vessel adjacent to superotemporal retinal nerve fiber layer thinning in a glaucoma suspect, suggesting vascular changes may precede structural loss. Weakness in the author's approach include the very small sample size (five glaucoma, eight suspect, six control) likely hiding baseline differences among groups and the invasive nature of erythrocyte mediated velocimetry (EMV) measurements requiring IV angiography with reinjected ICG-loaded erythrocytes. Future studies of EMV biomarkers would benefit from better understanding their statistical power of detection and translation to clinical outcomes.
The novel data presented by Chen et al. demonstrating retinal arteriole dysfunction in glaucoma patients adds specific confirmation of small blood vessel dysfunction, further eliciting the need for large scale longitudinal studies on vascular biomarkers and glaucoma progression with specific emphasis on understanding ischemia's impact on localized tissue and vision loss.