GLAUCOMA TREATMENT

Learn about the various classes of glaucoma treatment using medications, how they act and what you should know about precautions and side effects.

The main risk factor for the development of glaucoma is elevated intraocular pressure. Glaucoma treatment medications therefore target lowering it as their goal.

AQUEOUS HUMOR AND INTRAOCULAR PRESSURE

A fluid that fills and circulates through the front part of the eye called aqueous humor is produced in the ciliary body. This structure is located in the posterior chamber of the eye, behind the iris and in front of the lens.

Aqueous humor circulates first through the posterior chamber and then enters the anterior chamber of the eye through the pupil. Once it has circulated through the anterior chamber, the aqueous humor is drained through a structure known as the trabecular meshwork before retuning to the bloodstream through Schlemm's canal. In addition to exit through the trabecular meshwork, approximately 5-10% of aqueous humor exits the eye through an alternative route called the uveoscleral pathway.

The accumulation of excess aqueous humor in the interior of the eye is the cause of elevations in intraocular pressure and a number of strategies have been developed to address this area of glaucoma treatment. Primary among these are facilitating drainage of aqueous humor through the trabecular meshwork or uveoscleral pathway and retarding its production by the ciliary body.

The most common route of administration for glaucoma treatment medications is through an eye drop. There also are adjunct medications taken orally or parenterally, meaning by intramuscular or intravenous injection. However, parenteral administration always is a transient (short term) glaucoma treatment.

GUIDELINES FOR TAKING EYE DROPS

Tears continuously are produced in our eyes by structures called lacrimal glands.

Approximately 80% of the drug reaching the lacrimal duct is absorbed systemically, meaning that it enters the bloodstream. This is responsible for many of the side effects associated with glaucoma treatment medications administered through an eye drop.

Based on this information, it is essential to understand the following points.

• Although it might seem like most of the eye drop streams down your face, enough of it is absorbed through the cornea to be effective.
• It is unnecessary to apply a second drop into each eye. One is sufficient. Exceptions to this include if you miss the eye completely with the first drop or if for some reason your eye is shut completely before the drop is applied.
• You can limit medication side effects using a procedure called nasolacrimal duct occlusion. This is accomplished by applying slight pressure to the inner canthus of the eye, the region that is closest to the nose (see photo).

  Courtesy of Laboratorios Sophia SA de CV. © 2010.

  In the inner canthus, you will encounter a structure that is shaped like a grain of rice. Press it to the bone while applying the eye drop. This serves to block most of the medication from entering the nasolacrimal pathway for absorption into the blood. This will decrease the intensity of systemic side effects that the medicine may cause. It also ensures that more of the medication will stay in the eye for absorption.

GLAUCOMA MEDICATIONS

Glaucoma treatment medicines can be grouped according to the mechanism by which they lower intraocular pressure.

DRUGS THAT DECREASE THE PRODUCTION OF AQUEOUS HUMOR

These drugs act at the level of the ciliary body in the posterior chamber of the eye by decreasing the production of aqueous humor.

1. Beta-blockers. These are called first-line drugs, because they have good local (eye) and systemic (body) tolerance. The medications are in wide use and many have been available for 30 years. Examples include:
   • Timolol Maleate Ophthalmic Solution 0.5% (Timoptol^®, Istalol^®, Betimol^® )
   • Timolol maleate ophthalmic gel forming solution 0.25%, 0.5% (Timoptic-XE^®)
   • Timolol hemihydrate 0.25%, 0.5% (Betimol^®)
   • Betaxolol HCL ophthalmic solution 0.25%, 0.5% (Betoptic^® S)
   • Levobunolol HCL ophthalmic solution, USP 0.25%, 0.5% (Betagan^®)
   • Metipranolol ophthalmic solution 0.3% (OptiPranolol^®)
   • Carteolol HCL ophthalmic solution 1% (Ocupress^®)

   These medications can be combined with others for maximum effect and easier application.

   • Brimonidine Tartrate and Timolol Maleate (Combigan^TM)
   • Dorzolomide HCL and Timolol Maleate ( Cosopt^® )
2. Carbonic anhydrase inhibitors. This group includes some medicines that are administered through an eye drop.
   • Dorzolamide HCL ophthalmic solution 2% (Trusopt^®)
   • Brinzolamide ophthalmic suspension 1% (Azopt^TM)

   Some carbonic anhydrase inhibitors also can be administered orally.

   • Acetazolamide (Diamox^®, Sequels^®)

These medications act by enhancing aqueous humor drainage through the trabecular meshwork.

1. Adrenergic agonists. Known as selective alpha-2 blockers, these drugs have a dual function. They decrease aqueous humor production in the ciliary body and increase its drainage through the trabecular meshwork.
   • Brimonidine tartrate 0.1%, 0.15% (Alphagan^® P)
   • Apraclonidine HCL 0.5%, 1% (Iopidine^®)
2. Parasympathetic or cholinergic agents.
• Pilocarpine HCL ophthalmic solution 0.5%, 1%, 2%, 4%, 6%, 8% (Isopto^® Carpine, Pilocar^®)
• Carbachol 0.75%, 1.5%, 3% (Isopto^® Carbachol)
• Pilocarpine HCL gel 4% (Pilopine HS^® Gel)
• Pilocarpine-Epinephrine (E-Pilo-1, E-Pilo-2, E-Pilo-4, E-Pilo-6, P1E1, P2E1, P3E1, P4E1, P6E1)
• Physostigmine Sulfate (Eserine Sulfate^®)
• Echothiophate Iodide 0.03%, 0.125% (Phospholine Iodide^®)
3. Sympathomimetic agents
   • Epinephrine HCl (Epifrin)
   • Epinephryl Borate (Epinephryl Borate)
   • Dipivefrin Hcl (Propine-C Cap)

These medications act by enhancing aqueous humor drainage through the uveoscleral pathway. In this group are drugs known as prostaglandin analogues. They are the newest class of medicines and quickly have become first-line drugs because of their effectiveness.

• Travoprost 0.004% (Travatan^®, Travatan^® Z)
• Latanoprost 0.005% (Xalatan^®)
• Bimatoprost 0.03% (Lumigan^®)
• Unoprostone 0.150% (Rescula^®)

These are known as hyperosmotic agents. They cause vitreous humor to leave the eye through osmosis, a process in which water molecules move from an area of higher concentration to an area of lower concentration by passing through a membrane. Hyperosmotic agents are used in cases when other medications have not been effective in lowering intraocular pressure. Hyperosmotic treatment always is administered in a hospital under close medical supervision. This is because dosage must be calibrated on an individual basis and throughout the treatment. Additionally, a variety of adverse effects can occur that must be monitored. For this reason, hyperosmotic treatment is tolerated only for a short time. Moreover, its repeated use can result in decreased effectiveness.

• Mannitol
• Urea
• Glycerin

REFERENCE:

Damji KF, Freedman S, Moroi SE, and Rhee D. Shields Textbook of Glaucoma, 6th Ed. Philadelphia, PA: Lippincott, Williams and Wilkins, 2010.

Shaarawy TM, Sherwood MB, Hitchings RA, and Crowston JG. Glaucoma Volume 1: Medical Diagnosis and Therapy. New York: Elsevier, 2009.

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