Impact of Timolol/Dorzolamide Therapy on Autoregulation in Glaucoma Patients
Status:
Unknown status
Trial end date:
2015-05-01
Target enrollment:
Participant gender:
Summary
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.