The distinguishing feature of angle closure glaucoma is that the iridocorneal angle, the junction between the iris and the cornea, which functions as the site of aqueous humor outflow, is obstructed. The most common cause of primary angle closure is referred to as “pupillary block.” In order to understand the pathophysiology involved with pupillary block, it is important to understand the flow of aqueous in a nondiseased state (Figure 47.1). Aqueous humor is secreted from the ciliary body, a circumferential structure located behind the iris in the posterior chamber of the eye, and flows through the pupil to the anterior chamber of the eye. Eventually, the aqueous humor exits the
anterior chamber through the iridocorneal angle, which is composed of multiple layers of tissue. The most superficial layer is called the trabecular meshwork, a sievelike tissue with the deepest layer, called the canal of Schlemm. Through the canal of Schlemm, the aqueous humor ultimately drains into the venous system.

In pupillary block, the flow of aqueous humor from posterior to anterior chamber is blocked at the pupil, typically because there is contact between the lens and the iris. As the lens opacifies and grows with age (ie, cataract), the propensity of pupillary block to occur increases. As the aqueous accumulates behind the iris, the pressure in the posterior chamber increases, causing the iris to bow anteriorly, creating an outlet obstruction and perpetuating the cycle of angle closure.

Outside of pupillary block, the etiology of angle closure glaucoma can be subdivided into three other groups: physiologic crowding of the angle, lens induced, and plateau iris syndrome.³ Crowded angle tends to occur in patients with thicker iris tissue. In these cases, there is less space for aqueous humor to drain through the trabecular meshwork. With pupillary dilation, the iris is pulled peripherally and further crowds the iridocorneal angle. Lens-induced angle closure can occur either when a large, mature cataract pushes the iris forward and closes the angle or when the lens is subluxed anteriorly. In both cases, there may still be an element of pupillary block owing to the lens-iris contact, but the primary mechanism of angle closure is anterior displacement of the iris by the lens. In lens subluxation, the zonules, ligaments that suspend the lens in its anatomic position behind the iris, are loosened and cause the lens to displace anteriorly. Predisposing conditions for lens subluxation include trauma, Marfan syndrome, Ehlers-Danlos syndrome, and homocystinuria. Plateau iris syndrome is defined by an anterior insertion of the peripheral iris base onto the ciliary body. This positioning of the iris can cause narrowing of the iridocorneal angle that is not caused by pupillary block and can present as acute or chronic angle closure.³

Medication-induced angle closure glaucoma can be accounted for by a variety of mechanisms (pupillary block via miosis, angle crowding with mydriasis, and iridocorneal angle disruption secondary to ciliochoroidal effusion). Alpha-adrenergic agonists are mydriatic agents that are routinely administered by ophthalmologists and optometrists for pupillary dilation and funduscopic examination and are also found in a variety of over-the-counter cold and allergy medicines such as decongestants. Mydriasis induces thickening at the base of the iris that can potentially generate iridotrabecular contact and angle closure acutely. Anticholinergic agents such as atropine, tropicamide, and cyclopentolate target different muscles; however, all result in pupillary dilation and iridocorneal angle closure. Other medications that may precipitate angle closure glaucoma include beta₂ agonists, sulfonamide containing medications such as topiramate and trimethoprim-sulfamethoxazole, anticoagulants such as heparin and warfarin, and certain serotonergic agents.⁴