Pulsatile flow into the aqueous veins: manifestations in normal and glaucomatous eyes

Abstract

The aqueous outflow system is unique because nowhere else can the pattern of flow of an extravascular fluid be directly observed as it returns to the vascular system. Such observations reveal that aqueous flow both from Schlemm's canal into the aqueous veins and from the aqueous veins into the episcleral veins is pulsatile. Pulsatile aqueous flow mechanisms are observable in vivo not only in normal and but also in glaucomatous eyes. A series of specific patterns accompany the pulsatile mixing of aqueous with blood in the episcleral veins. These directly observable patterns of pulsatile flow are synchronous with intraocular pressure (IOP) transients induced by the cardiac pulse, blinking and eye movement. Patterns of pulsatile flow are altered by events that increase IOP such as pressure on the side of the eye, tonography and water drinking. Pulsatile flow stops when IOP is reduced below its resting level, but begins again when IOP returns to the resting level. Pulsatile flow reduction probably results from the intrinsic reduction of pulse amplitude at a lower IOP, and may thus provide a passive mechanism to maintain short-term homeostasis. Thus modulation of the pulsatile flow phenomenon appears to maintain a homeostatic IOP setpoint. Visible pulsatile flow abnormalities develop in glaucoma patients. Medications that reduce IOP through improvement in outflow do so through pulsatile flow mechanisms. Laboratory studies have demonstrated that cyclic stresses in outflow tissues alter signaling pathways, cytoskeletal responses, extracellular matrix composition and cytokine secretion. How physiologic pulse transients orchestrate cellular responses and how cellular responses identified in the laboratory may in turn regulate pulsatile aqueous outflow is unknown. Linkage of laboratory and in vivo observations await an improved understanding of how cellular and extracellular structures within the outflow system are able to generate an aqueous pulse wave. The purpose of the current report is to provide a summary of in vivo IOP-induced patterns of cyclic flow that can be used as part of a framework for interpretation of responses to cyclic stresses identified in the laboratory.

Fig. 1

Comparison between (IOP–EVP) and ocular transients. Mean intraocular pressure (IOP) in the population is ~16 mm Hg and episcleral venous pressure (EVP) is ~8 mm Hg. The difference between IOP and EVP (IOP–EVP) is thus ~8 mm Hg and represents the baseline hydrostatic pressure gradient driving aqueous flow from the eye. Ocular transients of the cardiac pulse, blinking and eye movements superimpose relatively large cyclic IOP gradients on the underlying baseline IOP–EVP gradient. Ocular transient IOP amplitudes from data reported by Coleman and Trokel (1969).

Fig. 2

(Panel A – Systole) Cardiac source of pulsatile flow. Systole-induced choroidal vasculature expansion (red arrows). Transient IOP increase (large black arrows). Aqueous pulse wave distends the trabecular meshwork (TM) forcing it outward into Schlemm’s canal (SC). One-way channels into SC prevent backflow (small curved arrows). Distention of the TM into SC reduces SC volume. SC pressure increases. Small black arrow denotes aqueous discharge from SC. Aqueous pulse wave then enters the aqueous vein. (Panel A – Diastole) Blood enters the left ventricle (green circle of arrows). Double red arrows indicate absence of a pressure wave in diastole. TM moves inward during diastole (green arrows). Aqueous enters SC (large blue arrow). (Panel B) During diastole episcleral venous pressure (EVP) is slightly higher than aqueous vein pressure (AVP), resulting in a relative EVP ↑). The EVP ↑ causes episcleral vein blood to move toward (B 1) or into (B 2–5) the aqueous mixing vein. The next systole causes a transient AVP ↑. The oscillations result in pulsatile flow manifestations in the aqueous veins. The AVP ↑ causes transient movement of a standing aqueous wave into a tributary episcleral vein (B 1), transient elimination of a lamina of blood (B 2), a bolus of blood swept into the increased aqueous stream (B 3), an oscillating increase in diameter of the aqueous component of a persistent laminar (B 4) or trilaminar (B 5) aqueous flow wave. Panel A is adapted from data of Phillips et al. (1992). Panel B adapted from observations of De Vries (1947) and Ascher (1961). (With kind permission from Springer: The Glaucoma Book, Aqueous Veins and Open Angle Glaucoma, 2010, pg. 68, Johnstone et al., Fig. 7.4.). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Distribution of visible aqueous veins. Two to three aqueous veins are typically visible in an eye although there may be a maximum of four to six. Distribution is highly assymetric with the majority of visible aqueous veins at or below the horizontal midline, the greatest number being present in the nasal quadrant. Derived from data of De Vries (1947).

Fig. 4

Evidence of Schlemm’s canal origin of pulsatile flow summarized in Ascher’s treatise (Ascher, 1961). Episcleral vein (ESV).

Fig. 5

Illustration of characteristic pulsatile flow changes caused by increasing IOP or addition of medications. Still frames and illustrations derived from video images of 59-year-old male. Increase in intraocular pressure (IOP) followed a water-drinking test but typifies pulsatile flow increase from other causes such as medications. (Panel A) Baseline IOP, velocity (V) is low and aqueous pulse wave travel (D) with each stroke is small. A standing transverse interface of aqueous and blood oscillates resulting in systolic discharge of aqueous into a small venous tributary (ST). (Panel B) An increased distance of travel of the oscillatory aqueous fluid wave. (Panel C) Increased velocity and travel of the aqueous fluid wave. At each systole a lamina of clear aqueous discharges into an episcleral vein. (Panel D) Velocity and travel of the fluid wave increase further. Continuous oscillating laminar flow is present in a more distal episcleral vein. Two hours after drinking water, IOP was again 10 mm Hg and stroke volume returned to appearance seen in Panel A. (With kind permission from Springer: The Glaucoma Book, Aqueous Veins and Open Angle Glaucoma, 2010, pg. 67, Johnstone et al., Fig. 7.2.)