Pigmentary Glaucoma Medication

Updated: Nov 12, 2021
  • Author: Lauren S Blieden, MD; Chief Editor: Hampton Roy, Sr, MD  more...
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Medication

Medication Summary

Although glaucoma is not simply a disease of elevated intraocular pressure (IOP), current medical therapy remains directed at lowering IOP.

A rational approach to choosing antiglaucoma medication should minimize the number of medications and probability of significant adverse effects.

As mechanisms of axonal death by apoptosis become better understood, therapies may be developed to protect nerve fibers from ongoing damage and death. This has been termed neuroprotection.

Agents currently under investigation as neuroprotective include glutamate receptor blockers, calcium channel blockers, inhibitors of nitric oxide synthase, free radical scavengers, and drugs to increase blood flow to the optic nerve. At the date of this article, no medications are currently approved for neuroprotection.

Bimatoprost, travoprost, latanoprost, and tafluprost are ophthalmic prostaglandin analogs approved in the United States. Bimatoprost is a prostamide analog with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Travoprost, latanoprost, and tafluprost are prostaglandin F2-alpha (ie, dinoprost) analogs. They are selective FP prostanoid receptor agonists believed to reduce IOP by increasing uveoscleral outflow. They are indicated for the lowering of IOP in patients with open-angle glaucoma or ocular hypertension who are intolerant of other IOP-lowering medications or who are insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another IOP-lowering medication. Latanoprostene bunod is a newer option that contains latanoprost acid to act on the traditional targets of the prostaglandin pathways and butanediol mononitrate which promotes the release of nitric oxide to relax the trabecular meshwork and decrease resistance to outflow. 

All prostaglandin analogues are administered once daily at bedtime (ie, 1 gtt in affected eye[s] hs). Travoprost has been studied in pediatric patients.

These medications are contraindicated if hypersensitivity has been documented. No drug interactions have been reported. All are classified as pregnancy category C (ie, safety for use during pregnancy has not been established).

All topcial prostaglandin analogues demonstrate the unusual adverse effect of permanent increase in pigment of the iris (ie, increases brown pigment) and eyelid, and they may increase eyelash growth. Bacterial keratitis may occur. Use is cautioned in uveitis or macular edema. They should not be used if inflammation is present.

Aqueous Suppression

Some glaucoma medications target the production of aqueous humor, the fluid that is produced by the ciliary body that flows through the anterior chamber and out the trabecular meshwork. These classes of medication lower eye pressure by decreasing aqueous humor production, and include topical beta-blockers, topical and oral carbonic anhydrase inhibitors, and topical alpha2-agonists.

Alpha-agonists are useful in pigmentary glaucoma, but the development of allergy in as many as 50% of patients precludes the long-term use of dipivefrin, epinephrine, and apraclonidine in many individuals. Brimonidine tartrate 0.2% may provide satisfactory IOP with less allergic reaction than other drugs in this class.

Topical carbonic anhydrase inhibitors are useful agents for treating pigmentary glaucoma and are generally well tolerated. Systemic agents should be reserved for particularly difficult circumstances or when the risks of surgery are unacceptably high.

Topical beta-blocker are generally well-tolerated and can be dose daily or twice a day. Caution must be used in patients that have reactive airway disease, like asthma or COPD, as well as in diabetics where beta-blockers may mask the sytemic symptoms of hypoglycemia. 

Rho-kinase Inhibitors

Rho-kinase inhibitors are a newer class of topical glaucoma medications that are well tolerated. The only approved rho-kinase inhibitor in the United States currently is netarsudil. The mechanism of action focuses on the actin-myosin filaments within the trabecular meshwork. Rho-kinase inhibitors prevent contraction of this filaments and relax the trabecular meshwork, decreasing resistance to outflow. These medications also decrease episcleral venous pressure, likely through a relaxation of smooth muscle fibers in the vascular outflow system causing vasodilation.

 

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Alpha-adrenergic agonists

Class Summary

Topical adrenergic agonists (sympathomimetics) decrease aqueous humor secretion.

Brimonidine (Alphagan)

Brimonidine is a relatively selective alpha2 adrenergic-receptor agonist that decreases IOP by dual mechanisms, reducing aqueous humor production and increasing uveoscleral outflow. Brimonidine has minimal effect on cardiovascular and pulmonary parameters. A moderate risk of allergic response to this drug exists. Caution should be used in individuals who have developed an allergy to Iopidine. IOP lowering of up to 27% has been reported.

Apraclonidine (Iopidine)

Apraclonidine is a potent alpha adrenergic agent that is selective for alpha2 receptors, with minimal cross-reactivity with alpha1 receptors. It suppresses aqueous production and reduces elevated, as well as normal, IOP, whether accompanied by glaucoma or not. Apraclonidine does not have significant local anesthetic activity. It has minimal cardiovascular effects.

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Beta-blockers

Class Summary

Topical beta-adrenergic receptor antagonists decrease aqueous humor production by the ciliary body. Adverse effects are due to systemic absorption of drug (decreased cardiac output and bronchoconstriction). In susceptible patients, this may cause bronchospasm, bradycardia, heart block, or hypotension. Monitor patient's pulse rate and blood pressure; patients may be instructed to perform punctal occlusion after administering the drops. Depression or anxiety may be experienced in some patients, and sexual dysfunction may be initiated or exacerbated.

Levobunolol (Betagan)

Nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production.

Timolol ophthalmic (Betimol, Istalol, Timoptic, Timoptic XE)

Nonselective beta-blocker. Timolol may reduce elevated and normal IOP, with or without glaucoma, by reducing the production of aqueous humor. Timolol gel-forming solution (Timoptic XE) usually is administered at night, unless it is used concurrently with latanoprost therapy. Used as 0.25% or 0.5% solution and applied topically to the eye 1-2 times per day.

Betaxolol ophthalmic (Betoptic S)

This agent selectively blocks beta1 adrenergic receptors, with little or no effect on beta2 receptors. It lowers IOP by reducing the production of aqueous humor. The drug may have less effect on the pulmonary system. Its IOP-lowering effect is slightly less than that of nonselective beta blockers. It may increase optic nerve perfusion and confer neuroprotection.

Carteolol ophthalmic

Blocks beta1-receptors and beta2-receptors and has an intrinsic sympathomimetic activity (partial agonist activity), with possibly less adverse effect on cardiac and lipid profiles.

Metipranolol

Beta-adrenergic blocker that has little or no intrinsic sympathomimetic effects and membrane stabilizing activity. Has little local anesthetic activity. Reduces IOP by reducing production of aqueous humor.

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Carbonic anhydrase inhibitors

Class Summary

Reduce secretion of aqueous humor by inhibiting carbonic anhydrase (CA) in the ciliary body. In acute angle-closure glaucoma, administer systemically; apply topically in patients with open-angle glaucoma. These drugs are less effective, and their duration of action is shorter than many other classes of drugs. Adverse effects are relatively rare but include superficial punctate keratitis, acidosis, paresthesias, nausea, depression, and lassitude.

Dorzolamide (Trusopt)

Used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one ophthalmic drug is being used, administer the drugs at least 10 min apart. Presumably, it slows bicarbonate ion formation, producing a subsequent reduction in sodium and fluid transport. In addition, reversibly inhibits CA, reducing hydrogen ion secretion at renal tubule, and increases renal excretion of sodium, potassium bicarbonate, and water to decrease production of aqueous humor.

Brinzolamide (Azopt)

Catalyzes reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. May use concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, administer drugs at least 10 min apart.

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Miotic agents (parasympathomimetics)

Class Summary

Constriction of the pupillary sphincter increases relative pupillary block and reduces iridolenticular contact. These drugs also contract the ciliary muscle, tightening trabecular meshwork and allowing increased outflow of aqueous. Adverse effects include brow ache, induced myopia, and decreased vision in low light.

Pilocarpine ophthalmic (Pilocar, Pilagan)

Also available as Pilogel, a naturally occurring alkaloid, pilocarpine mimics muscarinic effects of acetylcholine at postganglionic parasympathetic nerves. Stimulates salivary glands and smooth muscle, decreasing aqueous production and increasing outflow.

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Prostaglandin analogs

Class Summary

Prostaglandin analogs increase uveoscleral outflow of aqueous. One mechanism of action may be through the induction of metalloproteinases in the ciliary body, which breaks down the extracellular matrix, reducing resistance to outflow through the ciliary body. They can be used in conjunction with beta-blockers, alpha-agonists, or topical CA inhibitors. Many patients respond well to these agents; others do not respond at all. Adverse effects include iris pigmentation, cystoid macular edema, and uveitis.

Latanoprost (Xalatan, Xelpros)

Latanoprost may decrease IOP by increasing the outflow of aqueous humor. Patients should be informed about possible cosmetic effects to the eye/eyelashes, especially if uniocular therapy is to be initiated.

Bimatoprost (Latisse, Lumigan)

This agent is a prostamide analogue with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Bimatoprost ophthalmic solution is used to reduce IOP in open-angle glaucoma and ocular hypertension.

Travoprost ophthalmic (Travatan Z)

This agent is a prostaglandin F2-alpha analogue. It is a selective FP prostanoid receptor agonist that is believed to reduce IOP by increasing uveoscleral outflow. Travoprost ophthalmic solution is used to treat open-angle glaucoma and ocular hypertension.

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Carbonic anhydrase inhibitor / beta-blocker combination

Class Summary

A combination solution may decrease aqueous humor secretion more than would each solution used as monotherapy, while improving compliance

Dorzolamide hydrochloride/timolol maleate (Cosopt)

CA inhibitor that may decrease aqueous humor secretion, causing a decrease in IOP. Presumably slows bicarbonate ion formation with subsequent reduction in sodium and fluid transport.

Timolol is a nonselective beta-adrenergic receptor blocker that decreases IOP by decreasing aqueous humor secretion. Both agents administered together bid may result in additional IOP reduction compared with either component administered alone, but reduction is not as much as when dorzolamide tid and timolol bid are administered concomitantly.

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