Impact of Timolol/Dorzolamide Therapy on Autoregulation in Glaucoma Patients

Glaucoma is an optic neuropathy in which the main risk factor is intraocular pressure (IOP). The search for other variables involved in glaucoma pathogenesis and progression has identified both systemic and ocular signs of vascular dysfunction in glaucoma patients, such as migraine, peripheral vasospasm, systemic hypotension and cerebral microvascular ischemia. Ocular blood flow studies using Color Doppler Imaging (CDI) technology has demonstrated blood velocities and increased vascular resistance (RI) to exist in such patients when compared to healthy controls. However, a CDI examination provides far more additional information, such as arterial pulsatility (PI) and mean blood velocities (MFV). While these have been used for decades now to study cerebral arteries vasoreactivity, little is known about how these variables are changed in glaucoma patients. We have recently demonstrated that these variables can be used to identify a change in the normal vascular activity when there is increased resistance. In glaucoma patients, a cutpoint in RI of the retrobulbar arteries could be determined beyond which PI increased significantly. This sharp increase in the PI has been used as an indirect signal that the vessel's ability to buffer a decreased perfusion pressure has been surpassed. The normal response to a decreased perfusion in a vascular territory with autoregulation is an increase in dilation in the downstream microcirculation, increasing cross section area in an attempt to keep a steady MFV. As PI is calculated using the vessel's MFV [PI = (PSV-EDV)/MFV], it is highly sensitive to changes in this variable. As such, the cutpoints we have identified in glaucoma patients are therefore an indirect assessment of the vessel's autoregulation limit.

While our data could provide the rational as to why these RI values are associated with progression, the clinical question arises as to whether these cutpoints can be modulated by topical glaucoma therapy. As some medications such as carbonic anhydrase inhibitors have been found to have a positive effect in disease progression in what appears to be a non-IOP related effect, we considered the hypothesis that these drugs could have a positive impact on the ocular's microcirculation vasoactive response, potentially enabling to keep a steady MFV into higher values of vascular resistance.