Glaucoma is a complex disease characterized by an increase in intraocular pressure that, if sufficiently high and persistent, leads to damage to the optic disc at the juncture of the optic nerve and the retina; irreversible blindness can result.
Of the three types of glaucoma—primary, secondary, and congenital—anti-AChE agents are of value in the management of the primary as well as of certain categories of the secondary type (e.g., aphakic glaucoma, following cataract extraction); congenital glaucoma rarely responds to any therapy other than surgery.
Primary glaucoma is subdivided into narrow-angle (acute congestive) and wide-angle (chronic simple) types, based on the configuration of the angle of the anterior chamber where the aqueous humor is reabsorbed. Narrow-angle glaucoma is nearly always a medical emergency in which drugs are essential in controlling the acute attack, but the long-range management is often surgical (e.g., peripheral or complete iridectomy). Wide-angle glaucoma, on the other hand, has a gradual, insidious onset and is not generally amenable to surgical improvement; in this type, control of intraocular pressure usually is dependent upon continuous drug therapy.
Muscarinic stimulants and cholinesterase inhibitors reduce intraocular pressure by causing contraction of the ciliary body so as to facilitate outflow of aqueous humor and perhaps also by diminishing the rate of its secretion.
In the past, glaucoma was treated with either direct agonists (pilocarpine, methacholine, carbachol) or cholinesterase inhibitors (physostigmine, demecarium, echothiophate, isoflurophate). For chronic glaucoma, these drugs have been largely replaced by topical β blockers and prostaglandin derivatives.
Acute angle-closure glaucoma is a medical emergency that is frequently treated initially with drugs but usually requires surgery for permanent correction. Initial therapy often consists of a combination of a direct muscarinic agonist and a cholinesterase inhibitor (eg, pilocarpine plus physostigmine) as well as other drugs. Once the intraocular pressure is controlled and the danger of vision loss is diminished, the patient can be prepared for corrective surgery (iridectomy). Open-angle glaucoma and some cases of secondary glaucoma are chronic diseases that are not amenable to traditional surgical correction, although newer laser techniques appear to be useful.