Trabecular outflow

Aqueous humor exiting the eye through the trabecular pathway first crosses the trabecular meshwork, enters the Schlemm canal, passes through collector channels in the outer wall of the Schlemm canal, which drain either directly into aqueous veins or into the vessels of the intrascleral plexus, which then drain into aqueous veins. From there, aqueous humor returns to the systemic circulation via the episcleral venous system, which connects to the anterior ciliary and superior ophthalmic veins, ultimately draining into the cavernous sinus.

The trabecular meshwork is classically divided into 3 layers: (1) uveal, (2) corneoscleral, and (3) juxtacanalicular (Fig 2-2). The uveal trabecular meshwork is adjacent to the anterior chamber and is arranged in bands that extend from the iris root and the ciliary body to the peripheral cornea. The corneoscleral meshwork consists of sheets of trabeculum that extend from the scleral spur to the lateral wall of the scleral sulcus. The juxtacanalicular meshwork, which is thought to be the major site of outflow resistance, is adjacent to and actually forms the inner wall of the Schlemm canal. Aqueous humor moves both across and between the endothelial cells lining the inner wall of the Schlemm canal.

Figure 2-2 Trabecular meshwork and Schlemm canal. A, Three layers of the trabecular meshwork (TM; shown in cutaway views): uveal, corneoscleral, and juxtacanalicular. B, Anterior segment optical coherence tomography image of the TM and Schlemm canal.

(Part A modified with permission from Shields MB. Textbook of Glaucoma. 3rd ed. Williams & Wilkins; 1992; part B courtesy of Syril K. Dorairaj, MD.)

The trabecular meshwork is composed of multiple layers, each of which consists of a collagenous connective tissue core covered by a continuous endothelial layer. The trabecular meshwork is the site of pressure-sensitive aqueous humor outflow and functions as a 1-way valve, permitting aqueous humor to leave the eye by bulk flow but limiting flow in the other direction, independent of energy. The cells of the trabecular meshwork are phagocytic, and this function may increase in the presence of inflammation and after laser trabeculoplasty.

In most older adults, the trabecular cells contain a large number of pigment granules in their cytoplasm, giving the entire meshwork a pigmented appearance, the degree of which can vary with position in the meshwork and among individuals. There are approximately 200,000–300,000 trabecular cells per eye. With age, the number of trabecular cells decreases, and the basement membrane beneath them thickens, potentially increasing outflow resistance. An interesting effect of all types of laser trabeculoplasty is that it induces division of trabecular cells and causes a change in the production of cytokines and other structurally important elements of the extracellular matrix. The extracellular matrix material is found throughout the dense portions of the trabecular meshwork.

The Schlemm canal is completely lined with an endothelial layer that rests on a discontinuous basement membrane. The canal is a single channel, typically with a diameter of about 200–300 μm, although there is significant variability, and it is traversed by tubules. The exact path of aqueous flow across the inner wall of the Schlemm canal is uncertain. Intracellular and intercellular pores suggest bulk flow, while so-called giant vacuoles that have direct communication with the intertrabecular spaces suggest active transport; however, these vacuoles may be artifacts of tissue preparation and microscopy. The outer wall of the Schlemm canal is formed by a single layer of endothelial cells that do not contain pores.

A complex system of collector channels connects the Schlemm canal to the aqueous veins, which in turn drain into the episcleral veins, forming the distal portion of the trabecular outflow system (Video 2-1). The episcleral veins subsequently drain into the anterior ciliary and superior ophthalmic veins. These, in turn, ultimately drain into the cavernous sinus.

Courtesy of Alex Huang, MD, PhD.

Go to www.aao.org/bcscvideo_section10 to access all videos in Section 10.

The trabecular outflow pathway is dynamic. With increasing IOP, the cross-sectional area of the Schlemm canal decreases, while the trabecular meshwork expands. Similarly, in the distal outflow system, the amount of aqueous humor flow through individual vessels appears to vary dynamically. The effect of these changes on outflow resistance is unclear.

• Johnson M. What controls aqueous humour outflow resistance? Exp Eye Res. 2006;82(4):545–557.

Uveoscleral outflow

In the normal eye, any nontrabecular outflow is termed uveoscleral, or unconventional, outflow. Uveoscleral outflow is also referred to as pressure-insensitive outflow. Although it is pressure insensitive, uveoscleral outflow is bulk flow that depends on a pressure gradient that remains relatively constant with changes in IOP. Various mechanisms are probably involved in uveoscleral outflow, but the predominant one is passage of aqueous humor from the anterior chamber into the interstitial spaces between the ciliary muscle bundles and then into the supraciliary and suprachoroidal spaces. From there, the exact path of the aqueous humor exiting the eye is unclear. It may include passage through the intact sclera or along the nerves and vessels that penetrate it or may involve absorption into the vortex veins. Lymphatic vessels have also been identified in the ciliary body, and aqueous humor drainage through a uveolymphatic pathway has also been proposed.

• Johnson M, McLaren JW, Overby DR. Unconventional aqueous humor outflow: a review. Exp Eye Res. 2017;158:94–111.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.