Vascular Aspects in Glaucoma: From Pathogenesis to Therapeutic Approaches

Abstract

Glaucomatous optic neuropathies have been regarded as diseases caused by high intraocular pressure for a long time, despite the concept of vascular glaucoma dating back to von Graefe in 1854. Since then, a tremendous amount of knowledge about the ocular vasculature has been gained; cohort studies have established new vascular risk factors for glaucoma as well as identifying protective measures acting on blood vessels. The knowledge about the physiology and pathophysiology of the choroidal, retinal, as well as ciliary and episcleral circulation has also advanced. Only recently have novel drugs based on that knowledge been approved for clinical use, with more to follow. This review provides an overview of the current vascular concepts in glaucoma, ranging from novel pathogenesis insights to promising therapeutic approaches, covering the supply of the optic nerve head as well as the aqueous humor production and drainage system.

Keywords: blood flow; glaucoma; intraocular pressure.

Figure 1

(a) Different areas of perfusion of the optic nerve head showing a superficial nerve fiber layer, (b) prelaminar region, (c) laminar region, (d) retrolaminar region, (1) central retinal artery, (2) central retinal vein, (3) retina, (4) choroid, (5) sclera, (6) circle of Zinn-Haller, (7) short posterior ciliary arteries, (8) optic nerve sheath (9) subdural cavity, (10) arachnoid mater, (11) subarachnoidal space, (12) pia mater, (13) optic nerve.

Figure 2

Ocular Starling resistor. (A) Vessel flow (F) is a function of the pressure gradient (P1—P2) along the vessel divided by the resistance. (B,C) If the vessel passes through an organ (e.g., the eye) with a low tissue pressure (e.g., IOP), the pressure inside the vessel exceeds the pressure outside the vessel (i.e., the transmural pressure gradient) and so the vessel remains distended. (D,E) If the tissue pressure is somewhat higher and exceeds the pressure at the lowest point inside the vessel (i.e., at the “venous” end), that region of the vessel will begin to collapse. This will increase the resistance to flow in that segment, thereby raising the intraluminal pressure until the transmural pressure becomes slightly positive again. (F) If the tissue pressure becomes greater than the arterial input pressure, the vessel will collapse completely, the resistance will be infinite, and flow through the vessel will cease. Reproduced with permission from [18].

Figure 3

Relationship between intraocular pressure (IOP) and choroidal venous pressure (P choroid). As expected by the Starling resistor effect, choroidal venous pressure slightly exceeds intraocular pressure at medium to high IOP values. At lower IOP values, however, choroidal venous pressure deviates from this 1:1 relationship significantly, reaching 50% at values below 10 mmHg (unpublished observation by Reitsamer). Each dot represents a single pressure measurement, the red line represents a curve-fit of all measurement values.