eMedicine Specialties > Ophthalmology > Intraocular Pressure

Glaucoma, Pigmentary

Robert Ritch, MD, Chief of Glaucoma Service, Surgeon Director, Professor, Department of Ophthalmology, New York Eye and Ear Infirmary
Yaniv Barkana, MD, Consulting Staff, Glaucoma Unit, Department of Ophthalmology, Assaf Harofe Medical Center

Updated: Nov 6, 2007

Introduction

Background

Pigment dispersion syndrome (PDS) is an autosomal dominant disorder characterized by disruption of the iris pigment epithelium (IPE) and deposition of pigment granules on the structures of the anterior segment. Pigment granule accumulation in the trabecular meshwork then leads to progressive trabecular dysfunction and ocular hypertension with or without associated glaucomatous optic neuropathy. Because the age of onset often is in the third or fourth decade of life, this disorder is an important and often underdiagnosed glaucoma affecting younger people.

Pigmentary glaucoma (PG) originally was considered rare. In 1949, Sugar and Barbour described 2 young, myopic men with Krukenberg spindles, hyperpigmented trabecular meshworks and open angles, whose intraocular pressures (IOPs) increased with mydriasis and decreased with pilocarpine.¹ Investigations over the ensuing decades elucidated further features, including bilaterality, association with myopia, and a greater incidence in males.

While primary open-angle glaucoma (POAG) usually begins after age 40 years, PDS and PG typically affect younger individuals. The diagnosis of elevated IOP at a young age should prompt the examiner to search for a cause.

Myopia is an important risk factor for the development of PDS and is present in approximately 80% of affected individuals. Patients with higher degrees of myopia and deeper anterior segments tend to develop glaucoma at an earlier age. In patients with asymmetric disease, the more affected eye usually is the eye that is more myopic.

PDS appears to be autosomal dominant with incomplete penetration, the phenotype expression of which appears to be increased by the presence of myopia. Several pedigrees have been described with multiple affected members, and at least 1 genetic locus on chromosome band 7q35 has been identified.

Pathophysiology

The classic triad of clinical signs of PDS consists of a Krukenberg spindle, slitlike, radial, midperipheral iris transillumination defects, and pigment deposition on the trabecular meshwork. The iris tends to have a concave configuration and often inserts into the posterior ciliary body band.

Liberated pigment granules are borne by aqueous currents and deposited on the structures of the anterior segment. The vertical accumulation of these pigment granules along the corneal endothelium is known as a Krukenberg spindle. The spindle tends to be slightly decentered inferiorly and wider at its base than its apex. The spindle generally appears as a central, vertical, brown band up to 6 mm long and up to 3 mm wide. With time, it becomes smaller and lighter and often requires careful examination to identify it.

Frequency

United States

This condition is less common than open-angle glaucoma.

Mortality/Morbidity

If disease is not controlled, cupping of optic disk and reduction of visual field can occur.

Race

Pigment dispersion glaucoma affects Caucasians almost exclusively.

Sex

A higher incidence occurs in males.

Age

Onset usually occurs before age 40 years.

Clinical

History

Patients usually are asymptomatic.

Physical

Many patients with pigment dispersion glaucoma remain undetected, while those patients with glaucoma are misdiagnosed more often than not as having juvenile-onset glaucoma or POAG. Those patients without elevated IOP may have the presence of Krukenberg spindles noted, but they often are told that they have normal eye examinations and are not cautioned regarding possible future consequences of or the hereditary nature of the syndrome. Phenotypic expression varies, and some manifestations may be extremely subtle or perhaps not expressed at all, leading to lack of detection in a large segment of affected persons. Finally, many emmetropes and hyperopes, particularly prior to the onset of presbyopia, never undergo formal eye examinations, and even less frequently are they examined by ophthalmologists.

• Movement of the posteriorly bowed concave iris along the anterior zonular fibers results in the characteristic iris transillumination defects. This finding is pathognomonic for PDS. It is best to search for iris transillumination defects prior to pupillary dilation by using a small slit beam in a darkened room. However, those patients who do not appear to have transillumination defects on retroillumination but have increased trabecular pigmentation, Krukenberg spindle, myopia, or juvenile open-angle glaucoma can be examined with scleral transillumination using a fiberoptic scleral transilluminator in a darkened room to facilitate detection. Infrared video pupillography also is useful to determine the extent of the defects.
• Pigment accumulation on the anterior surface of the iris often appears as concentric rings within the iris furrows. More diffuse pigmentation can cause a diffuse darkening of iris color, which is more apparent in lightly pigmented irides because of the degree of color change. Asymmetric pigment liberation may result in iris heterochromia, with the darker iris being the more affected side.
• Pigment deposition in the trabecular meshwork typically produces a homogenous, densely pigmented band (mascara line). In older patients, in whom the trabecular meshwork begins to recover and the pigment gradually clears, the pigment band may become darker superiorly more than inferiorly, a pattern referred to as the pigment reversal sign. In these patients, it may be the only sign that suggests previous pigment dispersion. In such cases, examination of these patients' children may be confirmatory.
• Pigment may also accumulate at the zonular attachments to the lens, where it may form a Zentmayer ring.
• Patients with PDS and PG are at increased risk for retinal detachment, which may occur in as many as 6-7% of individuals. It has been suggested that retinal breaks and lattice degeneration occur twice as frequently in these eyes when compared to age and refraction-matched controls and are independent of the use of miotics and degree of myopia.

Causes

As described by Campbell in 1979, mechanical contact between the concave posterior iris surface and anterior zonular packets is responsible for the release of pigment granules from the IPE.² Histopathologic study and electron microscopy have confirmed the location of the iris defects to correspond closely to the position of the zonular packets. Whether a defect of the IPE in PDS contributes to their rupture or whether the release is due to mechanical forces alone is not known.

• Greater pigment liberation tends to occur in eyes with more pronounced iris concavity, presumably because of the closer proximity of the IPE to the zonules. The insertion of the iris into the ciliary body has been reported to be more posterior in PDS than in control eyes, an anatomic variation which places the IPE into closer proximity to the zonular apparatus and may increase the likelihood of iridozonular contact and zonular pigment dispersion. Trabecular endothelial damage and meshwork dysfunction lead to elevated IOP in susceptible individuals.
• Active pigment liberation typically occurs in patients in their third and fourth decades in life. As affected individuals age, increased pupillary miosis and cataract formation cause a slow increase in relative pupillary block, which increases resistance of aqueous flow from the posterior chamber, through the pupil, and into the anterior chamber. This permits accumulation of aqueous within the posterior chamber and increases the distance between the zonules and the iris. This may result in either a decrease or resolution of active pigment release by decreasing iridozonular contact.
• Continued phagocytosis of existing pigment in the trabecular meshwork may result in better aqueous outflow, improving IOP control. Lichter and Shaffer observed a definite decrease in the amount of meshwork pigment in 10% of 102 patients and concluded that the pigment could pass out of the meshwork as the patient aged.³ Older patients presenting with glaucoma may have only very subtle manifestations, if any, of PDS, and may be diagnosed to have POAG or low-tension glaucoma.
• Reverse pupillary block
  • Iridozonular contact occurs in PDS because the iris has a concave configuration, which brings it into closer approximation to the zonular apparatus. Since iris position changes with fluid pressure gradients within the anterior segment, the concept of reverse pupillary block has developed to explain the anatomic abnormalities, which lead to the iris concavity.
  • In reverse pupillary block, aqueous humor pressure is greater in the anterior chamber than in the posterior chamber. This is the opposite of relative pupillary block seen in angle-closure glaucoma, in which resistance to aqueous flow through the pupil causes the iris to move anteriorly and close the angle. Pupillary block angle-closure is relieved by laser iridectomy, which allows aqueous to move freely through the iridectomy into the anterior chamber, relieving the pressure gradient across the iris and opening the angle.
  • Reverse pupillary block could occur if an aliquot of aqueous were to be introduced suddenly into the anterior chamber and then trapped there, so as to be unable to equilibrate with aqueous in the posterior chamber. The increased pressure within the anterior chamber forces the iris against the lens, creating a flap valve that maintains the pressure differential between the chambers by preventing movement of aqueous back into the posterior chamber. The relative pressure difference between the 2 chambers would cause the iris to assume a concave configuration.
  • A concave iris configuration caused by a relative pressure differential between the anterior and posterior chambers is not unique to PDS. In iris retraction syndrome, increased uveoscleral outflow facilitated by retinal pigment epithelium–assisted fluid absorption in the presence of a retinal break causes the pressure within the posterior segment and the posterior chamber to be less than that of the anterior chamber. Eyes with iris retraction syndrome have extensive posterior synechiae preventing free flow of anterior chamber fluid into the posterior chamber. During routine phacoemulsification, posterior movement of the lens-iris diaphragm during the irrigation at the time of insertion of the phacoemulsification handpiece may be in part caused by a rapid increase in anterior chamber volume, which forces the iris against the lens surface. Because of this flap-valve effect, fluid cannot move into the posterior chamber, and the entire lens-iris diaphragm may move posteriorly.
• Blinking
  • Lid blinking may have a prominent contributory influence on iris configuration, and, thus, on the distribution of aqueous humor in the anterior segment. In 1994, Chew proposed that a blink initially deforms the cornea, transiently increasing IOP (in both the anterior and posterior chambers), and pushes the iris posteriorly against the lens.⁴ Immediately following the blink, pressure within the posterior chamber exceeds that of the anterior chamber and a small aliquot of aqueous moves into the anterior chamber along this pressure gradient. This causes the anterior chamber pressure to exceed that of the posterior chamber for a brief period. This momentary pressure gradient causes the iris to become concave and push it against the lens, preventing aqueous from flowing back into the posterior chamber (reverse pupillary block). The presence of cornea deformation during blinking has been reported in animal studies.
  • Increased iridolenticular contact and myopia, both present in PDS, appear to enhance the flap-valve effect of iris-lens contact, which helps to prevent equilibration of pressure between the 2 chambers. In non–pigment dispersion syndrome eyes, this reverse pupillary block mechanism is less complete and less able to maintain the pressure differential.
  • When blinking is prevented, aqueous secretion gradually increases the volume of the posterior chamber. As the volume and the pressure of the posterior chamber increase relative to the anterior chamber, the iris gradually flattens, iridolenticular contact diminishes, and iridozonular and iridociliary process distances increase.
• Accommodation and iris configuration: A concave iris configuration indistinguishable from that associated with PDS can be induced by accommodation in young, healthy individuals. During accommodation, contraction of the ciliary ring causes the lens to move forward slightly, which shallows the anterior chamber. The displaced aqueous cannot move into the posterior chamber because of the flap-valve effect; therefore, it is forced into the angle recess. Aqueous humor, now trapped in the anterior chamber, is forced into the angle recess and the peripheral iris assumes a concave configuration. This process is similar to the change in iris and angle configuration, which occurs during indentation gonioscopy.
• Exercise-induced pigment liberation: Pharmacologic pupillary dilation may result in marked pigment liberation accompanied by a rise in IOP. The same phenomenon may occur in some patients with PDS during strenuous exercise, particularly exercise involving jarring movements, such as jogging or basketball. Pretreatment with low-dose pilocarpine prior to exercise can limit both the pigment liberation and the IOP spike. Laser iridectomy (see Surgical Care) may not completely eliminate exercise-induced pigment liberation.

Differential Diagnoses

Glaucoma, Angle Recession
Glaucoma, Aphakic And Pseudophakic
Glaucoma, Drug-Induced
Glaucoma, Juvenile
Glaucoma, Plateau Iris
Glaucoma, Primary Open Angle

Other Problems to Be Considered

PDS usually can be distinguished easily from most other abnormalities in which dissemination of pigment is part of the disease process because no other condition that results in the characteristic iris transillumination defects exists. Other disorders associated with signs of pigment dispersion in the disruption of melanoma cells (eg, melanomalytic dispersion), cysts of the iris and ciliary body, postoperative conditions (eg, intraocular lens–iris chafing), and exfoliation syndrome often occur unilaterally.

Recently, an increase of PDS and PG secondary to iris chafing by intraocular lenses that were implanted in the ciliary sulcus, leading to the removal of the lens and/or trabeculectomy in some cases, has been reported.⁵ Phakic intraocular lenses can also result in PDS and PG. In these conditions, trabecular pigmentation is often less dense and is usually unevenly distributed throughout the circumference of the meshwork. Occasionally, pigment granules in the anterior chamber may be confused with inflammatory cells, leading to a misdiagnosis of uveitis.

The disease process most similar to PG is exfoliation glaucoma. In this condition, a loss of pigment occurs from the IPE, iris transillumination, pigment dispersion in the anterior segment, including Krukenberg spindle, trabecular pigmentation, and IOP elevation. The clinical history combined with a careful slit lamp biomicroscopic examination easily separates the 2 diseases.

The age of onset for exfoliation glaucoma is usually older than 60 years, and onset is rare in persons younger than 40 years. No sexual or racial predilection exists for exfoliation syndrome, although reports seem to indicate a higher prevalence of the disease in individuals of Scandinavian ancestry.

Meshwork pigmentation in exfoliation glaucoma is not as intense as in PG. Iris transillumination characteristically begins at the pupillary border and not the midperiphery. Unlike PDS, approximately 50% of patients with exfoliation syndrome are affected clinically in only 1 eye. Finally, the presence of white flakes of exfoliation material at the pupillary border and on the anterior lens surface is diagnostic of exfoliation syndrome.

Pigmentation of trabecular network

• Elderly individuals (inferior nasal or faint band circumstantial)
• Pseudoexfoliation of lens with or without glaucoma (unilateral or bilateral)
• Pigmentary glaucoma
• Krukenberg spindle without glaucoma
• Malignant melanoma (1 eye)
• Cyst of pigment layer or iris (unilateral)
• Previous intraocular operation, inflammation, or hyphema (scattered, mostly in lower angle)
• Nevus (dense, isolated patch)
• Open-angle glaucoma (patchy band, whole circumference)
• Following glaucoma irradiation for malignancy of nasal sinus

Pigment liberation into anterior chamber with dilation of pupil

• Diabetes mellitus (Willis disease)
• Exercise
• Hurler disease (mucopolysaccharidoses type IH)
• Low-tension glaucoma with pigment dispersion

Retrocorneal pigmentation

• Endothelial phagocytosis of free melanin pigment as Krukenberg spindle
• Iris melanocytes, iris pigment epithelial cells, or pigment-containing macrophages in the posterior corneal surface can follow operative or accidental ocular trauma
• Status post hyphema

Workup

Imaging Studies

• Ultrasound biomicroscopy (UBM) has been particularly useful in evaluating the structures surrounding the posterior chamber. UBM shows the posterior iris insertion⁶ , iris concavity, iridozonular contact, and extensive iridolenticular contact.

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.

Dosing

Adult

1 gtt OU bid

Pediatric

Not established; in pediatric age group, serious systemic adverse effects have been reported

Interactions

Coadministration with topical beta-blockers may further decrease IOP; tricyclic antidepressants may decrease effects of brimonidine; CNS depressants, such as barbiturates, opiates, and sedatives, may potentiate effects of brimonidine

Contraindications

Documented hypersensitivity; patients receiving MAOIs

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in cardiovascular disease, depression, cerebral or coronary insufficiency, orthostatic hypotension, and Raynaud syndrome

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.

Dosing

Adult

1 gtt tid

Pediatric

Not established

Interactions

Monitor pulse and BP frequently when giving cardiovascular drugs; not for use concurrently with MAOIs

Contraindications

Documented hypersensitivity; patients on MAOIs or have taken them in the past 14 d

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause an allergic contact dermatitis and follicular conjunctivitis; generally used in short-term therapy since efficacy may decrease over time

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.

Dosing

Adult

1 gtt bid

Pediatric

Not established

Interactions

Caution in systemic beta-blockers because the added dose may be sufficient to cause systemic adverse effects

Contraindications

Documented hypersensitivity; bronchial asthma; severe COPD; sinus bradycardia; second- and third-degree AV block; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-blockade may potentiate muscle weakness that is consistent with certain myasthenic symptoms (eg, diplopia, ptosis, generalized weakness); product may have sulfites, which may cause allergic-type reactions in certain susceptible persons

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.

Dosing

Adult

1 gtt bid

Pediatric

Not established

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; bronchial asthma; sinus bradycardia; second- and third-degree AV block; severe COPD; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Product may have sulfites, which may cause allergic-type reactions in susceptible patients

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.

Dosing

Adult

1 gtt bid

Pediatric

Not established

Interactions

May have additive systemic effects if patient is already on systemic beta-blockers

Contraindications

Documented hypersensitivity; bronchial asthma; severe COPD; sinus bradycardia; second- and third-degree AV block; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

As a beta1-selective agent, may be tried in patients with known reactive airway disease; bronchospasm may still occur; not as effective as other beta-blockers in lowering IOP; contraindicated in breastfeeding

Carteolol hydrochloride (Cartrol, Ocupress) 1%

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

Dosing

Adult

1 gtt bid

Pediatric

Administer as in adults

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; congestive heart failure; asthma; cardiac conduction defects; breastfeeding

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Product may have sulfites, which may cause allergic-type reactions in certain susceptible persons; contraindicated during breastfeeding

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.

Dosing

Adult

1 gtt bid

Pediatric

Not established

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; sinus tachycardia; cardiac failure; cardiogenic shock; second- and third-degree AV block

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in diabetes mellitus, bradycardia, asthma, cardiac failure, and AV block; contraindicated during breastfeeding

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.

Dosing

Adult

1 gtt bid; for Timoptic XE, 1 gtt qd

Pediatric

Not established

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; bronchial asthma; sinus bradycardia; second- and third-degree AV block; severe COPD; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Product may have sulfites, which may cause allergic-type reactions in susceptible patients; contraindicated during breastfeeding

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.

Dosing

Adult

1 gtt qd/bid

Pediatric

Not established

Interactions

Increases toxicity of beta- and alpha-blocking agents and that of halogenated inhalational anesthetics

Contraindications

Documented hypersensitivity; narrow- or shallow-angle glaucoma; aphakia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adverse effects include ocular irritation, conjunctival injection, and palpebral conjunctival follicle formation; systemic effects are rare but include tachycardia and hypertension

Dipivefrin (AKPro, Propine)

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

Dosing

Adult

1 gtt bid

Pediatric

Not established

Interactions

Increased or synergistic effects are seen when used concurrently with agents that lower IOP

Contraindications

Documented hypersensitivity; narrow angles; dilation of pupil may predispose patient to attack of angle-closure glaucoma

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Macular edema occurs in up to 30% of aphakic patients treated with epinephrine; discontinuation of treatment generally results in reversal of maculopathy; caution in vascular hypertension

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.

Dosing

Adult

1 gtt tid

Pediatric

Not established

Interactions

Coadministration with high-dose salicylate therapy may increase toxicity; may have additive systemic effects if patient is already on oral CA inhibitors

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause ocular discomfort, superficial punctate keratitis, or hypersensitivity reactions; to minimize adverse effects, patients may be started on a qd or bid dose and gradually advanced to tid dosing; contraindicated in breastfeeding

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.

Dosing

Adult

1 gtt tid

Pediatric

Not established

Interactions

May have additive systemic effects if patient is already on oral CA inhibitors

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Causes less ocular discomfort but also may cause foreign body sensation; local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with long-term administration of dorzolamide (discontinue therapy and evaluate patient before restarting therapy)

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.

Dosing

Adult

1 gtt bid

Pediatric

Not established

Interactions

Coadministration with high-dose salicylate therapy may increase toxicity; may have additive systemic effects if patient is already on oral CA inhibitors

Contraindications

Documented hypersensitivity; COPD; CHF; asthma; cardiac conduction defects

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with long-term administration of dorzolamide (discontinue therapy and evaluate patient before restarting therapy); product may have sulfites, which may cause allergic-type reactions in susceptible patients

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.

Dosing

Adult

1 gtt bid

Pediatric

Not established

Interactions

May be ineffective when used concomitantly with nonsteroidal anti-inflammatory agents

Contraindications

Documented hypersensitivity; miotics generally do not work well in secondary glaucomas (except exfoliation syndrome and pigment dispersion); may exacerbate ocular inflammatory disease and should not be used

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Warn patients that pilocarpine causes pupillary constriction and may cause decreased vision in presence of cataract; may cause aching pain in eye or artificial myopia due to increased accommodation

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.

Dosing

Adult

1 gtt qhs

Pediatric

Not established

Interactions

Coadministration with eye drops containing the preservative thimerosal may reduce effects (administer at intervals of 5 min between applications)

Contraindications

Documented hypersensitivity; CHF; asthma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not administer while wearing contact lenses; may increase brown pigment in iris and may change eye color gradually (unknown effect)

Follow-up

Further Outpatient Care

• Long-term monitoring is important to assess the effectiveness of the therapy.

Complications

• Long-term follow-up care is needed for patients with glaucoma to ensure control of the disease.

Prognosis

• Prognosis is favorable with control of IOP.

Patient Education

• Good patient education helps to ensure compliance with the treatment of this chronic disorder.
• For excellent patient education resources, visit eMedicine's Glaucoma Center. Also, see eMedicine's patient education article Ocular Hypertension, Glaucoma Overview, Glaucoma FAQs, and Understanding Glaucoma Medications.

Miscellaneous

Medicolegal Pitfalls

• Early diagnosis and timely treatment help maintain the best visual function.

References

1. Sugar HS, Barbour FA. Pigmentary glaucoma: a rare clinical entity. Am J Ophthalmol. 1949;32:90.

2. Campbell DG. Pigmentary dispersion and glaucoma. A new theory. Arch Ophthalmol. Sep 1979;97(9):1667-72. [Medline].

3. Lichter PR, Shaffer RN. Diagnostic and prognostic signs in pigmentary glaucoma. Trans Am Acad Ophthalmol Otolaryngol. Sep-Oct 1970;74(5):984-98. [Medline].

4. Chew SJ, Tello C, Wallman J, Ritch R. Blinking indents the cornea and reduces anterior chamber volume as shown by ultrasound biomicroscopy. Invest Ophthalmol Vis Sci. 1994;35 (Suppl):1573.

5. Uy HS, Chan PS. Pigment release and secondary glaucoma after implantation of single-piece acrylic intraocular lenses in the ciliary sulcus. Am J Ophthalmol. Aug 2006;142(2):330-2. [Medline].

6. Kanadani FN, Dorairaj S, Langlieb AM, Shihadeh WA, Tello C, Liebmann JM, et al. Ultrasound biomicroscopy in asymmetric pigment dispersion syndrome and pigmentary glaucoma. Arch Ophthalmol. Nov 2006;124(11):1573-6. [Medline].

7. Harasymowycz PJ, Papamatheakis DG, Latina M, De Leon M, Lesk MR, Damji KF. Selective laser trabeculoplasty (SLT) complicated by intraocular pressure elevation in eyes with heavily pigmented trabecular meshworks. Am J Ophthalmol. Jun 2005;139(6):1110-3. [Medline].

8. Cantor L. Section 10: Glaucoma. In: Basic and Clinical Science Course. American Academy of Ophthalmology: 1996-1997.

9. Chaudry I, Wong S. Recognizing glaucoma. In: A Guide for the Primary Care Physician. Vol 99. 1999:247-64.

10. Gupta N, Weinreb RN. New definitions of glaucoma. Curr Opin Ophthalmol. Apr 1997;8(2):38-41. [Medline].

11. Hitchings RA. Glaucoma: current thinking. Br J Hosp Med. Mar 20-Apr 2 1996;55(6):312-4. [Medline].

12. Liesegang TJ. Glaucoma: changing concepts and future directions. Mayo Clin Proc. Jul 1996;71(7):689-94. [Medline].

13. Qureshi IA. Effects of mild, moderate and severe exercise on intraocular pressure of sedentary subjects. Ann Hum Biol. Nov-Dec 1995;22(6):545-53. [Medline].

14. Reistad CE, Shields MB, Campbell DG, Ritch R, Wang JC, Wand M. The influence of peripheral iridotomy on the intraocular pressure course in patients with pigmentary glaucoma. J Glaucoma. Aug 2005;14(4):255-9. [Medline].

15. Shields MB. Textbook of Glaucoma. 4^th ed. 1998.

16. Siddiqui Y, Ten Hulzen RD, Cameron JD, Hodge DO, Johnson DH. What is the risk of developing pigmentary glaucoma from pigment dispersion syndrome?. Am J Ophthalmol. Jun 2003;135(6):794-9. [Medline].

17. Van Buskirk EM. Medicolegal aspects of glaucoma care. Surv Ophthalmol. Jul-Aug 1998;43(1):83-6. [Medline].

Keywords

pigmentary glaucoma, pigment dispersion syndrome, PDS, pigment granule accumulation, progressive trabecular dysfunction, ocular hypertension, glaucomatous optic neuropathy, PG, POAG, open angle, open-angle glaucoma, myopia

Contributor Information and Disclosures

Author

Robert Ritch, MD, Chief of Glaucoma Service, Surgeon Director, Professor, Department of Ophthalmology, New York Eye and Ear Infirmary
Robert Ritch, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Ophthalmological Society, Chinese American Medical Society, International College of Surgeons, New York Academy of Medicine, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Coauthor(s)

Yaniv Barkana, MD, Consulting Staff, Glaucoma Unit, Department of Ophthalmology, Assaf Harofe Medical Center
Yaniv Barkana, MD is a member of the following medical societies: Israel Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Andrew I Rabinowitz, MD, Consulting Staff, Department of Ophthalmology, Barnet Dulaney Perkins Eye Center
Andrew I Rabinowitz, MD is a member of the following medical societies: Aerospace Medical Association, American Academy of Ophthalmology, and American Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

Martin B Wax, MD, Clinical Professor, Department of Ophthalmology, University of Texas Southwestern Medical School; Vice President, Ophthalmology Research and Development, Head, Ophthalmology Discovery Research, Alcon Labs, Inc
Martin B Wax, MD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)