Pigmentary Glaucoma

Pigmentary Dispersion Syndrome and Pigmentary Glaucoma

Introduction

PDS and PG essentially represent the same spectrum of disease whereby pigment granules which normally adhere to the back of the iris (the colored part of the eye), flake off into the aqueous humor  and accumulate in the trabecular meshwork leading to progressive trabecular dysfunction and ocular hypertension, with or without associated glaucomatous optic neuropathy. This pigment granule accumulation is often caused by PDS which 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. When pressure spikes and damage to the optic nerve result from the above process, the condition of PDS is considered Pigmentary glaucoma (PG). Although the occurrence of PG is rare, it is often of rapid onset and because IOP may become very high, aggressive treatment is often necessary to get it under control.

According to the University of Michigan Kellogg Eye Center, in this type of glaucoma the iris of the eye moves backwards--instead of forward as in low-tension glaucoma. This backward movement disturbs the eye pigment cells, causing them to rub against the lens, which causes pigment particles to be released into the eye's drainage canal, thereby blocking the drainage route and causing an increase in the pressure of the eye.

Population primarily affected

PDS and/or PG often begins in the 20's to 40’s age group,  making younger people affected by this condition often under diagnosed. However, statistically the condition is considered rare.  PDS and PG almost exclusively affect whites and studies have shown that a higher incidence occurs in males. Although pigment dispersion syndrome appears to strike both men and women at an equal rate, researchers are investigating why men develop pigmentary glaucoma up to three times more often than women. Research has also shown this syndrome develops into pigmentary glaucoma at a younger age in men than in women. Myopia is an important risk factor for the development of pigment dispersion syndrome and is present in approximately 80% of those affected.

Pathophysiology

The main three distinguishing characteristics are 1) Dense trabecular pigmentation. 2) Iris translumination defects and 3) The deposition of pigment found on the posterior surface in the area of the central cornea.

Myopia as mentioned, is an important risk factor for the development of pigment dispersion syndrome and is present in approximately 80% of affected individuals. Myopic (nearsighted) eyes have a concave-shaped iris which creates an unusually wide angle. This causes the pigment layer of the eye to rub on the lens. This rubbing action causes the iris pigment to shed into the aqueous humor and onto neighboring structures, such as the trabecular meshwork. Pigment may disrupt the pores of the trabecular meshwork and interfere with drainage, thereby increasing the IOP.

According to glcuaoma specialist Dr. Robert Ritch of the New York Eye and Ear Institute in the article Pigmentary Glaucoma, “mechanical contact between the concave posterior iris surface and anterior zonular packets is responsible for the release of pigment granules from the iris pigment epithelium (IPE)”. He further elaborates that “Histopathologic study and electron microscopy have confirmed the location of the iris defects to closely correspond to the position of the zonular packets.” Whether a defect of the iris pigment epithelium in pigment dispersion syndrome 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 iris pigment epithelium to the zonules. The insertion of the iris into the ciliary body has been reported to be more posterior in pigment dispersion syndrome than in control eyes, an anatomic variation which places the iris pigment epithelium 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. Older patients presenting with glaucoma may have only very subtle manifestations, if any, of pigment dispersion syndrome, and may be diagnosed to have primary open-angle glaucoma or low-tension glaucoma.

•   Reverse pupillary block involves the following:

•   Iridozonular contact occurs in pigment dispersion syndrome 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 pigment dispersion syndrome. 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 hand piece 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.

•   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. 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 pigment dispersion syndrome, 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.

•   A concave iris configuration indistinguishable from that associated with pigment dispersion syndrome 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.

•   Pharmacologic pupillary dilation may result in marked pigment liberation accompanied by a rise in IOP. The same phenomenon may occur in some patients with pigment dispersion syndrome 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. ”

Diagnosis

The large pressure spikes associated with PG may become evident as halos around lights, blurred vision, or slight ocular pain. At the slit lamp, patients with PDS and PG demonstrate liberation of iris pigment within the anterior chamber. Often, this appears as a granular brown vertical band along the corneal endothelium (Krukenberg's spindle). Pigment dusting may be evident on the lens, the iris surface and Schwalbe's line. Gonioscopy may reveal dense pigmentation covering the trabecular meshwork for 360 degrees, most prominently in the inferior quadrant. The angle itself remains open, and in some cases appears atypically wide open as noted previously. Radial, spoke-like transillumination defects of the mid-peripheral iris are another common finding.

Treatment

The treatment of Pigmentary glaucoma usually involves pressure lowering eyedrops involving monotherapy or combination medications from the family of beta blockers, alpha blockers, or prostaglandins such as xalatan. Doctors may also use a class of drugs called miotics which constrict the pupil which can lower pressures and also prevent rubbing which results in the liberation of pigment. This happens as a result of pulling the peripheral iris away from the zonular fibers. Because miotics have side effects, they may not used as often as the other classes of drugs.

Another treatment in younger patients is a procedure called iridotomy which involves a laser that makes a hole in the iris. This can help relieve some of the anterior pressure resulting in the iris not being pushed back against the lens. However, this procedure has limitations and its use and effectiveness are still under scrutiny. Finally, laser procedures like SLT can be useful in improving the efficiency of the Trabecular meshwork to relieve pressure, but some studies suggest that extra care needs to be taken and lower energies used because of the higher light absorption due to the heavy pigment.