canal of Schlemm

**Anatomy and aqueous humor flow** - Aqueous humor is made by the nonpigmented epithelium of the ciliary body (ciliary processes), via carbonic anhydrase and active secretion. It is stimulated by beta-2 receptors. - Flow path: posterior chamber → through the pupil → anterior chamber → trabecular meshwork (in the iridocorneal angle) → canal of Schlemm → collector channels → episcleral veins → systemic venous circulation. - This is the conventional (trabecular) pathway, which accounts for most outflow. The uveoscleral pathway is a minor route (~10–20%). Aqueous passes through the ciliary muscle interstitium and exits through the sclera. Prostaglandin analogs increase this pathway. - The canal sits in the scleral sulcus at the corneoscleral junction, just peripheral to the trabecular meshwork and anterior to the scleral spur.

**Clinical significance** - **Primary open-angle glaucoma (POAG):** The angle is open, but resistance to outflow is increased in the trabecular meshwork and juxtacanalicular region, and sometimes in the canal itself. The result is gradual, painless, bilateral peripheral vision loss, with increased cup-to-disc ratio (optic nerve cupping) and elevated IOP. - **Angle-closure glaucoma:** The peripheral iris blocks the trabecular meshwork, so aqueous cannot reach the canal. Presentation is an acute, painful red eye with a mid-dilated, nonreactive pupil, halos, headache, nausea/vomiting, and a hazy cornea. This is an ophthalmologic emergency. Treatment includes acetazolamide, topical beta blockers, alpha-agonists, and pilocarpine, followed by laser peripheral iridotomy. - **Pharmacology tied to this pathway:** - Cholinergic agonists (pilocarpine, carbachol) contract the ciliary muscle, which opens the trabecular meshwork and increases outflow through the canal of Schlemm (used in open-angle and angle-closure). - Prostaglandin analogs (latanoprost, bimatoprost) increase uveoscleral outflow. Side effects include eyelash growth and iris pigmentation. - Beta blockers (timolol), alpha-2 agonists (brimonidine), and carbonic anhydrase inhibitors (acetazolamide, dorzolamide) decrease aqueous production. - Rho-kinase inhibitors (netarsudil) and other newer agents increase trabecular outflow. - **Procedures:** Selective laser trabeculoplasty (SLT) improves trabecular outflow. Minimally invasive glaucoma surgeries (MIGS) bypass or stent into the canal. - **Other associations:** Elevated episcleral venous pressure (e.g., Sturge-Weber syndrome, carotid-cavernous fistula) can reduce outflow through the canal, which causes secondary glaucoma. Blood can reflux into the canal and become visible on gonioscopy when episcleral venous pressure is high.

**High-yield pearls** - Canal of Schlemm = drain of the anterior chamber. Ciliary body = source of aqueous. - The eye has normal IOP of about 10–21 mmHg. - Open-angle = decreased outflow with a normal angle. Closed-angle = anatomical blockage of the trabecular meshwork by the iris. - Do not confuse with the canal of Cloquet (hyaloid canal, a remnant of the fetal hyaloid artery in the vitreous).