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Impairments of autoregulation and neurovascular coupling in the optic nerve head play a critical role in ocular pathologies, especially glaucomatous optic neuropathy. We critically review the literature in the field, integrating results obtained in clinical, experimental, and theoretical studies. We address the mechanisms of autoregulation and neurovascular coupling in the optic nerve head, the current methods used to assess autoregulation--including measurements of optic nerve head blood flow (or volume and velocity)--blood flow data collected in the optic nerve head as pressure or metabolic demand is varied in healthy and pathologic conditions, and the current status and potential of mathematical modeling work to further the understanding of the relationship between ocular blood flow mechanisms and diseases such as glaucoma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To study whether impaired retinal autoregulation is a risk factor for glaucoma, the relationship between vascular regulatory mechanisms and glaucoma progression needs to be investigated. In this study, a vascular wall mechanics model is used to predict the relative importance of regulatory mechanisms in achieving retinal autoregulation., Methods: Resistance vessels are assumed to respond to changes in pressure, shear stress, carbon dioxide (CO2), and the downstream metabolic state communicated via conducted responses. Model parameters governing wall tension are fit to pressure and diameter data from porcine retinal arterioles. The autoregulation pressure range for control and elevated levels of IOP is predicted., Results: The factor by which flow changes as the blood pressure exiting the central retinal artery is varied between 28 and 40 mm Hg is used to indicate the degree of autoregulation (1 indicates perfect autoregulation). In the presence of only the myogenic response mechanism, the factor is 2.06. In the presence of the myogenic and CO2 responses, the factor is 1.22. The combination of myogenic, shear, CO2, and metabolic responses yields the best autoregulation (factor of 1.10)., Conclusions: Model results are compared with flow and pressure data from multiple patient studies, and the combined effects of the metabolic and CO2 responses are predicted to be critical for achieving retinal autoregulation. When IOP is elevated, the model predicts a decrease in the autoregulation range toward low perfusion pressure, which is consistent with observations that glaucoma is associated with decreased perfusion pressure.