eMedicine Specialties > Ophthalmology > Intraocular Pressure

Glaucoma, Pigmentary: Treatment & Medication

Author: Robert Ritch, MD, Chief of Glaucoma Service, Surgeon Director, Professor, Department of Ophthalmology, New York Eye and Ear Infirmary
Coauthor(s): Yaniv Barkana, MD, Consulting Staff, Glaucoma Unit, Department of Ophthalmology, Assaf Harofe Medical Center
Contributor Information and Disclosures

Updated: Nov 6, 2007

Treatment

Medical Care

Although many individuals have PDS, fewer than one half will develop ocular hypertension or glaucoma. However, since PDS is a risk factor for the development of ocular hypertension, all patients with this disorder should undergo periodic eye examinations. This is particularly important during the pigment liberation phase of the disease. The frequency of follow-up care can be decreased when pigment liberation ceases or trabecular pigmentation begins to diminish.

• PDS typically is a bilateral disease, although asymmetry may occur. A correlation exists between the amount of pigment lost from the posterior surface of the iris, increased degree of pigmentation in the trabecular meshwork, and degree of dysfunction in the trabecular meshwork as evidenced by elevation of the IOP. The size and density of the Krukenberg spindle does not necessarily correlate with trabecular meshwork damage. However, the amount of pigment that is presented to the trabecular meshwork does play a role in the elevation of the IOP. Markedly asymmetric disease usually is due to an additional factor, making 1 eye worse, such as anisometropia or the development of exfoliation syndrome or angle recession, or an additional factor acting to prevent the development of PDS, such as aphakia or Horner syndrome.
• Progressive glaucomatous optic neuropathy in PG is primarily pressure dependent and reduction of IOP is the mainstay of therapy. In addition to monitoring of IOP, sequential ophthalmic examinations should include gonioscopy to assess the degree and progression of trabecular pigmentation, stereoscopic evaluation and photography of the optic nerve, and perimetry.
• Since the degree and stage of pigment liberation, IOP, and extent of glaucomatous optic neuropathy vary among individuals, each must be evaluated to determine the proper course of intervention. As understanding of the pathogenesis of pigment liberation expands, consideration also should be given to gearing therapy toward eliminating acute pigment release, rather than just treating elevated IOP.
• Beta-adrenergic antagonists: The mainstay of initial medical therapy for PG continues to be aqueous suppression with a topic beta-blocker, primarily because of the relatively easy dosing schedule and minimal side effects.
• Parasympathomimetics
  • In theory, therapy directed at increasing relative pupillary block should relieve iridozonular contact and diminish pigment liberation. The relief of iridozonular contact following miotic therapy has been demonstrated with UBM. Pupillary miosis increases resistance to aqueous flow from the posterior chamber, past the lens surface, and through the pupil into the anterior chamber. This increased resistance allows aqueous pressure to build within the posterior chamber (ie, relative pupillary block), and forces the iris to move anteriorly, away from the zonules, and assume a convex configuration. However, strong miotics in young individuals rarely are tolerated because of the associated spasm of accommodation and blurring of vision.
  • Low-dose pilocarpine, in the form of Ocusert, often provides enough miosis to create pupillary block, without disabling adverse effects. A careful peripheral retinal examination should be performed before and after the institution of or change in miotic therapy because of the higher incidence of retinal breaks and detachment in these patients.
• Alpha-adrenergic agonists: Alpha-agonists are useful in PG, but the development of allergy in up to 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.
• Carbonic anhydrase inhibitors: Topical carbonic anhydrase inhibitors are useful agents for treating PG and are generally well tolerated. Systemic agents should be reserved for particularly difficult circumstances or when the risks of surgery are unacceptably high.
• Prostaglandin analogs: Prostaglandin analogues, which lower IOP by increasing uveoscleral outflow are effective in treating PG and offer the advantage of once daily administration. The iris surface color change that may occur during therapy appears to involve increased melanin production by iris melanocytes and is not known to affect the IPE or result in pigment dispersion.

Surgical Care

• Laser trabeculoplasty: Argon laser trabeculoplasty may be offered as a treatment in the management of uncontrolled PG. Although the initial result is often good, a larger proportion of patients can lose control of IOP when compared to patients with POAG, and the loss of control can occur in less time. In contrast to other forms of open-angle glaucoma, younger patients appear to respond better to trabeculoplasty than older individuals. Selective laser trabeculoplasty has been reported to result in marked and sustained IOP elevation, necessitating trabeculectomy in a few eyes with pigmentary glaucoma; therefore, it should be used with great caution.⁷
• Laser iridectomy: Laser iridectomy eliminates the iris concavity present in most patients with PDS by permitting equalization of pressures between the anterior and posterior chambers. This causes the iris to become flat, thereby decreasing iridozonular contact and reversing the underlying anatomical defect, which results in pigment dispersion. Anecdotal evidence suggests that this can prevent continued pigment liberation, result in a reversal of trabecular pigmentation, and, subsequently, lower IOP. However, long-term lowering of IOP and stabilization of glaucomatous optic neuropathy and visual field loss have not been demonstrated conclusively. Although theoretically sound, laser iridectomy should be used with caution because of the paucity of data regarding the long-term efficacy of this procedure.
• Filtering surgery: The surgical management of patients with PG follows the same principles and considerations used in the management of POAG. The appearance and change in the optic nerve along with visual field defects should be the principal guidelines used in deciding whether surgery is needed. Most patients respond well to standard filtration operations, although antifibrosis agents may be indicated to achieve a low target pressure or for reoperation. No unusual problems typically are encountered during cataract surgery.

Medication

Despite the fact that glaucoma is not simply a disease of elevated IOP, current medical therapy is directed toward 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 the following: glutamate receptor blockers, calcium channel blockers, inhibitors of nitric oxide synthase, free radical scavengers, and drugs to increase blood flow to the optic nerve.

Bimatoprost (Lumigan), travoprost (Travatan), and unoprostone (Rescula) are new ophthalmic prostaglandin analogs recently 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 and unoprostone are prostaglandin F2-alpha (ie, dinoprost) analogs similar to latanoprost. 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 insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another IOP-lowering medication.

Bimatoprost and travoprost are each administered once daily at bedtime (ie, 1 gtt in affected eye[s] hs); whereas, unoprostone must be administered bid. They have not 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).

Like latanoprost, all 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.

Alpha-adrenergic agonists

Topical adrenergic agonists (sympathomimetics) decrease aqueous humor secretion.

Brimonidine (Alphagan)

Selective alpha2-receptor antagonist that reduces aqueous humor formation and possibly increases uveoscleral outflow.

Apraclonidine 0.5%, 1% (Iopidine)

Reduces IOP whether or not accompanied by glaucoma. Selective alpha-adrenergic agonist without significant local anesthetic activity. Has minimal cardiovascular effect.

Beta-blockers

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) 0.25%, 0.5%

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

Timolol hemihydrate (Betimol) 0.25%, 0.5%

May reduce elevated and normal IOP, with or without glaucoma, by reducing production of aqueous humor or by outflow.

Betaxolol (Betoptic) 0.25%, 0.5%

Beta1-selective adrenergic antagonist. Selectively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors. Reduces IOP by reducing production of aqueous humor.

Carteolol hydrochloride (Cartrol, Ocupress) 1%

Blocks beta1- and beta2-receptors and has mild intrinsic sympathomimetic effects.

Metipranolol (OptiPranolol) 0.3%

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.

Timolol maleate (Timoptic, Timoptic XE) 0.25%, 0.5%

Nonselective beta-blocker. May reduce elevated and normal IOP, with or without glaucoma, by reducing production of aqueous humor.

Sympathomimetics (epinephrine and dipivefrin)

Increase the outflow of aqueous humor through trabecular meshwork and possibly through uveoscleral outflow pathway, probably by a beta2-agonist action. Up to one third of patients will not respond to these drugs.

Epinephrine (Epifrin) 0.5%, 1%, 2%

Lower IOP by increasing outflow and reducing production of aqueous humor. Used as adjunct to miotic or beta-blocker therapy. Combination of miotic and sympathomimetic will have additive effects in lowering IOP.

Dipivefrin (AKPro, Propine)

Prodrug of epinephrine, designed to lower incidence of adverse effects.

Carbonic anhydrase inhibitors

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 hydrochloride (Trusopt) 2%

Used concomitantly with other topical ophthalmic drug products to lower IOP. If more than 1 ophthalmic drug is being used, administer the drugs at least 10 min apart. 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) 1%

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 1 topical ophthalmic drug is being used, administer drugs at least 10 min apart.

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.

Miotic agents (parasympathomimetics)

These drugs contract the ciliary muscle, tightening trabecular meshwork and allowing increased outflow of aqueous. Miosis results from action of these drugs on the pupillary sphincter. Adverse effects include brow ache, induced myopia, and decreased vision in low light.

Pilocarpine (Pilocar, Pilagan) 1%, 2%, 4%

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.

Prostaglandin analogs

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) 0.005%

May decrease IOP by increasing outflow of aqueous humor.

• Search for CME/CE on This Topic »

• Glaucoma, Complications and Management of Glaucoma Filtering (Ophthalmology)
• Glaucoma, Unilateral (Ophthalmology)
• Rubella (Pediatrics: General Medicine)
• Glaucoma, Primary Open Angle (Ophthalmology)

• Glaucoma Center
• Ocular Hypertension Overview
• Ocular Hypertension Causes
• Ocular Hypertension Symptoms
• Ocular Hypertension Treatment
• Glaucoma Overview
• Glaucoma FAQs
• Understanding Glaucoma Medications

• Implantable Lens Provides Predictable, Stable Correction of Moderate to High Myopia for 4 Years
• ARVO 2009: Trabeculectomy May Be More Effective Than Medical Therapy in Reducing Intraocular Pressure in Glaucoma Patients
• Glaucoma Patients Can Participate in Moderate Aerobic Exercise

• Highlights in Glaucoma From the 2008 World Ophthalmology Congress
• Bimatoprost/Timolol Fixed Combination Vs Latanoprost/Timolol Fixed Combination in Open-angle Glaucoma Patients
• Glaucoma and Depression

• Glaucoma Resource Center
• Pediatric Ophthalmology Resource Center