Evaluation of the effect of elevated intraocular pressure and reduced ocular perfusion pressure on retinal capillary bed filling and total retinal blood flow in rats by OMAG/OCT

Abstract

Purpose To determine if retinal capillary filling is preserved in the face of acutely elevated intraocular pressure (IOP) in anesthetized rats, despite a reduction in total retinal blood flow (RBF), using optical microangiography/optical coherence tomography (OMAG/OCT). Methods OMAG provided the capability of depth-resolved imaging of the retinal microvasculature down to the capillary level. Doppler OCT was applied to measure the total RBF using an enface integration approach. The microvascular pattern, capillary density, and total RBF were monitored in vivo as the IOP was increased from 10 to 100 mm Hg in 10 mm Hg intervals and returned back to 10 mm Hg. Results In animals with mean arterial pressure (MAP) of 102 ± 4 mm Hg (n = 10), when IOP was increased from 0 to 100 mm Hg, the capillary density remained at or above 80% of baseline for the IOP up to 60 mm Hg [or ocular perfusion pressure (OPP) at 40 mm Hg]. This was then decreased, achieving 60% of baseline at IOP 70 mm Hg and OPP of 30 mm Hg. Total RBF was unaffected by moderate increases in IOP up to 30 mm Hg, beyond which total RBF decreased linearly, reaching 50% of baseline at IOP 60 mm Hg and OPP 40 mm Hg. Both capillary density and total RBF were totally extinguished at 100 mm Hg, but fully recovered when IOP returned to baseline. By comparison, a separate group of animals with lower MAP (mean = 75 ± 6 mm Hg, n = 7) demonstrated comparable decreases in both capillary filling and total RBF at IOPs that were 20 mm Hg lower than in the initial group. Both were totally extinguished at 80 mm Hg, but fully recovered when IOP returned to baseline. Relationships of both parameters to OPP were unchanged. Conclusion Retinal capillary filling and total RBF responses to IOP elevation can be monitored non-invasively by OMAG/OCT and both are influenced by OPP. Retinal capillary filling was relatively preserved down to a perfusion pressure of 40 mm Hg, despite a linear reduction in total RBF.

A Period of Controlled Elevation of IOP (CEI) Produces the Specific Gene Expression Responses and Focal Injury Pattern of Experimental Rat Glaucoma

“…Given this level of systemic blood pressure, an IOP of 60 mm Hg provides a perfusion pressure of 40 mm Hg, which is sufficient to maintain retinal and ONH perfusion to at least 80% of baseline, as determined previously using optical coherence tomography angiography 56,60,61 and other methods. 62 Above 60 mm Hg, perfusion decreases rapidly.…”

“…We chose to use inhalational isoflurane as it produces excellent general anesthesia with minimal animal movement which, coupled with flexible tubing and specific features of the head holder, successfully minimized intraocular trauma. Because this agent can lower systemic blood pressure, we carefully monitored this parameter and found that, using the conditions described here, including active removal of waste gas and CO 2 , 56 mean blood pressure averaged 100 mm Hg. This is comparable to that reported in rats using isoflurane for shorter periods of time, as well as other anesthetics.…”

Angiographic and structural imaging using high axial resolution fiber-based visible-light OCT

“…3(C)). Inspection of the angiographic z-profile showed three distinct retinal plexuses: superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), resembling the axial vascular distribution of the human retina [51][52][53] and mouse retina [54]. Below Bruch's membrane, the flow signal from the choriocapillaris was detected.…”

Posterior rat eye during acute intraocular pressure elevation studied using polarization sensitive optical coherence tomography

“…OCT and its functional extensions hereby enable the determination of various structural and functional parameters in vivo. Retinal perfusion at various IOP levels was studied using OCT-based optical microangiography [17–19]. The ONH and the optic nerve itself were studied under physiological conditions [20] and after IOP elevation using conventional OCT [21,22].…”

“…deformation of the ONH, together with polarization properties such as scleral birefringence. Since earlier studies [17–19] already investigated the microvascular response to an acute IOP increase, we exclusively focus on changes of tissue morphology and polarization properties in this article. Furthermore, ex vivo micro-computed tomography (µCT) was performed to identify anatomical relations in and around the eye ball.…”