Glaucoma is an eye disease that, if untreated, can damage the optic nerve of the eye and result in permanent visual loss. It is usually associated with increased pressure within the eye (intraocular pressure, or IOP). Increased intraocular pressure results from either increased production or decreased drainage of aqueous humor, a clear fluid within the front of the eye. The resulting increase in pressure within the eye may eventually damage the optic nerve. This increase in intraocular pressure is by far the most common risk factor for vision loss due to glaucoma.
Glaucoma affects the optic nerve and may cause vision loss. The optic nerves of both eyes transmit electrical signals from the retinas of the eyes to the brain, allowing an individual to see. If the optic nerve does not function correctly, these electrical signals cannot get through, which results in vision loss, even though the rest of the eye is normal. If there is failure to diagnose glaucoma or if glaucoma is not adequately treated, damage to the optic nerve may result. This damage to the optic nerve will initially be manifested by subtle loss of side vision and, if the glaucoma remains untreated, ultimately may cause loss of central vision and total blindness. Vision loss from glaucoma is irreversible.
Treatment is designed to lower the IOP by reducing production or increasing outflow of aqueous humor. Depending on the type of glaucoma, medications or surgery are used. IOP usually can be lowered using different medications in the form of eyedrops and oral or IV medications.
Elevated intraocular pressure (IOP) is one of the most important risk factors for the development of glaucoma, which is a progressive optic neuropathy. Lowering IOP is currently the only therapeutic approach for glaucoma. Treatment is designed to reduce intraocular pressure (IOP) either by reducing production or increasing drainage of aqueous humor from the eye. Depending on the type of glaucoma, medications, surgery or a combination of the two, may be used. In most patients with glaucoma, intraocular pressure can be lowered by using different medications, primarily in the form of drops placed onto the surface of the eye.
Selective prostanoid FP-receptor (sensitive to prostaglandin F) agonists became generally available as eyedrops for the treatment of glaucoma in 1996. These include latanoprost (Xalatan), bimatoprost (Lumigan), travoprost (Travatan and Travatan-Z), unoprostone (Rescula), and tafluprost (Zioptan). The prostanoid group of eyedrops is the most commonly used first-line medication for the treatment of glaucoma. Latanoprost is currently available in a generic form.
How prostaglandins/prostanoids work: These drugs, administered as eyedrops, have an effect on the aqueous drainage system within the eye to increase aqueous outflow which, in turn, lowers intraocular pressure (IOP).
Who should not use these medications:
Use: These drugs are given as eyedrops to the affected eye(s).
Drug or food interactions: Eyedrops containing the preservative thimerosal form a crystal if administered at the same time. Wait at least five minutes between applications. If administered with pilocarpine eyedrops, wait at least 10 minutes -- preferably, one hour -- between applying the two drugs.
Side effects: These eyedrops should not be used while wearing contact lenses. An increase in brown pigment in the iris and gradual changes in eye color may occur. Eyelash growth and pigmentation may increase. Skin on the eyelids and around the eyes may darken. Variable loss of orbital fat has been reported. Excessive tearing, eye pain, or lid crusting may occur. Burning, stinging, foreign-body sensation (something in the eye), blurred vision, and itching have also been observed.
Beta adrenergic blockers, administered as eyedrops, became available in the late 1970s and quickly became the most commonly used drug for the treatment of glaucoma. Since the advent of the prostaglandin group of drugs, beta adrenergic locking drops have become the second most widely used therapy. This group includes timolol (Timoptic, Betimol, Istalol), levobunolol (Betagan, AKBeta), betaxolol (Betoptic), carteolol (Ocupress), and metipranolol (OptiPranolol). Timolol is currently available in a generic form.
How beta-blockers work: These drugs lower intraocular pressure by reducing the amount of aqueous humor produced.
Most adrenergic beta-blockers are nonselective and block both the beta-1 and beta-2 receptors. A nonselective blocker inhibits both heart muscle and opening of the airways of the lungs. These are, therefore, contraindicated in patients with asthma, emphysema, chronic obstructive pulmonary disease (COPD), bradycardia (low pulse rate), and congestive heart failure. Betaxolol (Betoptic) is a selective beta-1 receptor antagonist. Its mechanism of action is similar to timolol, but since it is a selective beta-1 blocker, it is better tolerated in patients with lung disease than is timolol.
Who should not use these medications:
Use: These drugs are administered as eyedrops to the affected eye(s).
Drug or food interactions: Ocular beta-blockers may have additive effects when used with oral beta-blockers. Additive effects occur when used with other drugs that lower intraocular pressure.
Side effects: Beta-blockers may contain sulfites, which may cause allergic-type reactions. Rarely, use may worsen or cause symptoms similarly observed with orally administered beta-blockers, such as heart disturbances (abnormal heart rhythm, heart attack, or heart failure), asthma, chronic obstructive pulmonary disease, impotence, or mental changes (especially in elderly persons).
Alpha agonists became available in the 1990s and are used today as third-line drugs, with prostanoids being first line and beta-blockers being second line. These include various formulations of brimonidine (Alphagan, Alphagan-P).
Alpha agonists work to both decrease production of fluid and increase drainage. Alphagan P has a purite preservative that breaks down into natural tear components and may be more effective for people who have allergic reactions to preservatives in other eyedrops. Brimonidine is currently available in a generic form.
Who should not use these medications:
Use: These drugs are given as eyedrops to the affected eye(s).
Side effects: These eyedrops should not be used while wearing contact lenses. Local allergic reactions are common, characterized by redness of the eyes and itching of the eyes. Excessive tearing, eye pain, or lid crusting may occur. Burning, stinging, foreign body sensation (something in the eye), blurred vision, and itching have also been observed.
Other adrenergic agents became available in the 1960s and are rarely used today, having been largely supplanted by alpha adrenergic agonists. These drugs lower intraocular pressure by reducing the amount of aqueous humor produced and also reduce resistance to outflow of aqueous humor. This class of eyedrops includes epinephrine (Eppy, Eppy-N) and dipivefrin (AKPro, Propine). Adrenergics may cause swelling of the macula (the center part of the retina) and eye irritation. They also may cause black deposits of the lining of the inside of the lids with extended use.
These drugs should not be used by individuals allergic to adrenergic eyedrops.
Carbonic anhydrase inhibitors were initially developed as agents to treat high blood pressure (hypertension) but then were found to also decrease intraocular pressure. They reduce the action of an enzyme called carbonic anhydrase, which is necessary for the production of aqueous fluid. The carbonic anhydrase inhibitors include the oral agents acetazolamide (Diamox) and methazolamide (Neptazane, GlaucTabs) and the eyedrops brinzolamide (Azopt) and dorzolamide (Trusopt). The pills are rarely used today for the treatment of either glaucoma or hypertension but are effective in the treatment of altitude sickness. The drops are currently used as fourth-line therapy in glaucoma and are often used in combination with other glaucoma drops.
Who should not use these medications:
Use: These drugs are given as eyedrops, pills, and for glaucoma emergencies, intravenously.
Drug or food interactions: When administered systemically, such as with pills or injections, carbonic anhydrase inhibitors may decrease therapeutic levels of lithium and alter the body's elimination of amphetamines, quinidine, phenobarbital, or aspirin.
Side effects: Individuals with liver disease may become comatose with oral administration. Eyedrops may cause irritation of the eyelids.
Miotics are eyedrops that stimulate the parasympathetic nervous system causing the pupil of the eye to become smaller. They reduce intraocular pressure by increasing the outflow of eye fluids from the eye and they are usually used to reverse angle-closure glaucoma or prevent angle-closure in eyes with narrow chamber angles. Pilocarpine (one of the miotics) has been used for almost 150 years for the treatment of glaucoma. It is rarely utilized today to treat open-angle glaucoma.
Miotic drops include pilocarpine (Ocusert Pilo-40, Pilocar, Pilagan, Piloptic, Pilostat), carbachol (Carbastat, Carboptic, Isopto Carbachol, Miochol and Miostat Intraocular), and echothiophate iodide ophthalmic (Phospholine Iodide).
Who should not use these medications:
Drug or food interactions: If administered with prostaglandin eyedrops, wait at least 10 minutes -- preferably, one hour -- between applying the two drugs.
Side effects: Miotics should be used with caution in persons with corneal abrasion(s) and in those with a history of retinal detachment.
Hyperosmotics are sugar-based liquids meant to be taken by mouth. Hyperosmotics are used in the treatment of acute-onset angle-closure glaucoma. The effects last only six to eight hours, so they are not for long-term use. Hyperosmotics include mannitol (Osmitrol), glycerin (Osmoglyn), and isosorbide (Ismotic).
Who should not use these medications:
Use: These drugs are given orally or can be given intravenously to rapidly correct high elevations of intraocular pressure.
Drug or food interactions: Hyperosmotics may decrease lithium levels.
Side effects: Hyperosmotics should be used with caution in people who have diseases worsened by salt retention.
Many patients with glaucoma require more than one type of medication for adequate control of their glaucoma. Combined eyedrop medications can offer an alternative for patients who need more than one type. In addition to the convenience of using one eyedrop bottle instead of two, there may also be a financial advantage, depending on the insurance plan. Cosopt is a combination of a beta-blocker (timolol) and a carbonic anhydrase inhibitor (Dorzolamide). Combigan combines an alpha agonist (brimonidine) with a beta-blocker (timolol). Simbrinza combines an alpha agonist (brimonidine) with a carbonic anhydrase inhibitor (Brinzolamide). Combinations of prostaglandin analogs and beta adrenergic blockers have been available in Europe for years but have not achieved FDA approval in the United States.
There are currently some new drug classes being tested for the reduction of intraocular pressure in glaucoma. The results of clinical trials will soon be reviewed by the FDA.
Latanoprostene bunod (Vesneo) is a potential glaucoma medication that combines a nitric oxide donating molecule with a prostaglandin analog. Rhopressa is a rho-kinase (ROCK) inhibitor that can decrease intraocular pressure by relaxing the drainage system of the aqueous. Other ROCK inhibitors are approved in Japan, but their use has been somewhat limited by the side effect of redness of the eye. Trabodenoson is the first of a new class of compounds known as selective adenosine mimetics. These appear to have minimal side effects in clinical trials to date.
A number of drugs, both oral and in drop form, have been studied to provide protection of the optic nerve from damage from elevated pressure in glaucoma. Such "neuro-protective" agents, if effective and approved, will offer an entirely different way to prevent visual loss from glaucoma.
REFERENCES:
"Primary Open-Angle Glaucoma (Preferred Practice Pattern)." American Academy of Ophthalmology. 2015.
Weinreb, Robert N., Tin Aung, and Felipe A. Medeiros. "The Pathophysiology and Treatment of Glaucoma: A Review." JAMA 311.18 (2014): 1901-1911.
