eMedicine Specialties > Ophthalmology > Intraocular Pressure

Glaucoma, Pigmentary

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

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.

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